Статті в журналах з теми "Nuclear modifi- cation factor"
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1
Sabirov, I. S., J. A. Murkamilova, A. I. Sabirova, I. T. Murkamilov, V. V. Fomin, and F. A. Yusupov. "Risk factors for cardiovascular complications in chronic kidney disease." Clinical Medicine (Russian Journal) 100, no. 9-10 (December 13, 2022): 432–38. http://dx.doi.org/10.30629/0023-2149-2022-100-9-10-432-438.
Повний текст джерелаАнотація:
Risk factors are constitutional peculiarity and human behavior that infl uence the disease development and / or pathological condition in the future. With regard to certain nosological units, including cardiovascular diseases, modifi able and nonmodifi able risk factors are distinguished. Non-modifi able risk factors for the development and progression of cardiovascular diseases include age, gender, and genetic predisposition, which are used to develop risk stratifi cation systems. These risk factors cannot be adjusted, ie. modifi ed, and can only be taken into account when determining the level of risk of diseases development. On the contrary, modifi able risk factors can undergo changes and be subdivided into behavioral and biological ones. Behavioral risk factors include: smoking, unhealthy diet, low physical activity, excessive alcohol consumption, chronic psycho-emotional stress. These behavioral risk factors in the lifestyle of a modern person are becoming more common in the conditions of urbanization, and contribute to the development of cardiovascular diseases. It should be noted that with longterm exposure to behavioral risk factors on the human body, biological risk factors are also formed: arterial hypertension, dyslipidemia, overweight, obesity, diabetes mellitus, chronic kidney disease.This review discusses the contribution of chronic kidney disease as a risk factor, as well as the mechanisms of formation and progression of cardiovascular diseases in kidney dysfunction.
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Kizilcan, Nilgun, and Merve Istif. "Novel comonomer synthesis from thiophene-2-carbonyl chloride and polydimethylsiloxane modified cyclohexanone formaldehyde resin." Pigment & Resin Technology 43, no. 5 (August 26, 2014): 277–84. http://dx.doi.org/10.1108/prt-07-2013-0055.
Повний текст джерелаАнотація:
Purpose – The purpose of this paper is to produce an electroactive monomer containing ketonic resins and then to investigate redox reaction between Fe+3 and bounded thiophene in comonomers. First, thiophene functionalised ketonic resins (Th-CFPDMSR) were synthesised by esterification reaction of thiophene-2-carbonyl chloride (ThCCl) and hydroxyl groups of cyclohexanone formaldehyde resin (CFR). Th-CFPDMSR was then polymerised by ferric salt. Thiophene modified ketonic resins (Th-CFPDMSR) as comonomers were characterised by common techniques such as gel permeation chromatography, proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimeter and scanning electron microscope. Design/methodology/approach – Th-CFPDMSR comonomers were synthesised by esterification reaction of ThCCl and hydroxyl groups of ketonic resins. Then, the in-situ chemical oxidation (ISCO) of ThC-CFR in the presence of iron (III) chloride salt (FeCl3) was accomplished in chloroform/acetonitrile mixture solutions at room temperature. Findings – Important structural factor determined quantitatively for Th-CFPDMSR is the CFPDMS/TCCl ratio after reaction. The mole ratio effect of TCCl and ketonic resin on the solubility, molecular weight, melting temperature (Tm) and glass transition temperature (Tg) values of the comonomers (TCCl-CFPDMSR) was investigated. Research limitations/implications – The ferric ion (Fe+3) has a standard oxidation potential. Furthermore, FeCl3 can react with thiophene to produce a cation radical. FeCl3 cannot react with hydroxyl groups of ketonic resins. When ferric is used for ISCO application at relatively low temperatures (e.g. < 20°C), the oxidation reactions are usually less aggressive. Practical implications – This work provides technical information for the synthesis of conducting block copolymer and for the synthesis of chain-extended resins. The modified resins contain thiophene. The chemical oxidation system has been used to polymerise these thiophene groups, and resins with much higher molecular weight might be produced. The resins may also promote the adhesive strength of a coating and corrosion inhibition to metal surfaces of a coating. Originality/value – Novel Th-CFPDMSR comonomers were synthesised. These comonomers have higher Tg and Tm values than CF-PDMSR alone. The chemical oxidation system has been used to polymerise these thiophene functionalised ketonic resins.
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Doschechkina, Irina. "The role of scale factor in the formation of prod-uct properties under the action of surface modifi-cation." Bulletin of Kharkov National Automobile and Highway University, no. 94 (December 16, 2021): 97. http://dx.doi.org/10.30977/bul.2219-5548.2021.94.0.97.
Повний текст джерелаАнотація:
Based on theoretical and experimental research in the fields of solid-state physics and physical materials science, it is proved that the surface layer of a solid body, which is deformed, is an independent functional subsystem and radically affects large-scale levels of plastic flow and destruction of the product as a whole. As is known, the most effective method of improving the performance of products is the grinding of grain, because it is the grain boundary (substructural) mechanism of strengthening which provides an increase in the structural strength of the product. In this regard, special attention is paid to submicro- and nano-structuring of the surface. Goal. The aim of the work is to study the process of structure formation of the surface layer under the action of ion bombardment (IB) and its effect on the properties of products taking into account the scale factor. To achieve this goal, the following tasks were set: to evaluate the characteristics of the surface microstructure after IB and to study its tensile behavior in cylindrical and flat samples of low-carbon steel in order to take into account the scale factor in changing their properties. The submicro-structuring of the surface by ion bombardment is carried out in the work and its influence on the behavior of products during tensile deformation is investigated. It is established that the presence of a thin modified layer (with a constant core) significantly changes the properties of the product under force. The decisive role belongs to the contribution of the surface layer (scale factor) – the ratio of the area of the modified layer to the volume of the product: if it is <1 the effect of hardening is better realized while maintaining plasticity, and if ˃ 1, it is a significant effect of plasticization which maintains (or even increases) hardening.
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KOZHEVNIKOV, YURIY A. "APPLICATION OF MICROALGAE CHLORELLA VULGARIS BY LIVESTOCK BREEDING ENTERPRISES." Agricultural engineering, no. 5 (2021): 31–35. http://dx.doi.org/10.26897/2687-1149-2021-5-31-35.
Повний текст джерелаАнотація:
Industrial production of microalgae phytomass from agricultural waste for energy production purposes can solve the internal energy supply and environmental issues in the farm sector. The closed-cycle energy supply scheme is used in the livestock breeding facility to get hot water, feed additives to the cattle diet, biohumus, motor biofuels, and carbon dioxide, which is advisable to use in microalgae cultivation. The article presents a study of the experimental process of microalgae cultivation in a photobioreactor. The study goal was to determine the infl uence of technological conditions on the productivity of microalgae and obtain initial data for the development of closed cycles of using the energy potential of algamass in the heat and power supply of farm enterprises (e.g. dairy and poultry farms etc.). The authors carried out experiments using a photobioreactor for microalgae cultivation with an intelligent control system. The developed photobioreactor diff ers from the conventional variants by the pulsating hydrodynamic mode of feeding the nutrient solution. This modifi cation increases the productivity of microalgae cultivation by up to 15%. The cultivation conditions of Chlorella vulgaris microalgae on combined nutrition showed a noticeable increase in crop productivity when adding cattle manure extract in the amount of 30 to 60% (vol.) to the nutrient medium. This factor can be used to design closed cycles of the rmal and electrical supply of cattle farms based on third-generation biofuels obtained from microalgae phytomass.
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Saborowski, Michael, Gerd A. Kullak-Ublick та Jyrki J. Eloranta. "The Human Organic Cation Transporter-1 Gene Is Transactivated by Hepatocyte Nuclear Factor-4α". Journal of Pharmacology and Experimental Therapeutics 317, № 2 (25 січня 2006): 778–85. http://dx.doi.org/10.1124/jpet.105.099929.
Повний текст джерела
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Tsuji, Masamichi, and Sridhar Komarneni. "Alkali metal ion exchange selectivity of Al-substituted tobermorite." Journal of Materials Research 4, no. 3 (June 1989): 698–703. http://dx.doi.org/10.1557/jmr.1989.0698.
Повний текст джерелаАнотація:
Alkali metal ion exchange isotherms at a total ionic strength of 0.001 M were determined at 25 °C on a 1.13 nm anomalous [Al3+ + Na+]-substituted tobermorite with the formula, Ca5Na0.75Al0.9Si5.1O16(OH)2 · 6.03H2O. The Kielland plots of Na+/K+, Na+/Rb+, and Na+/Cs+ exchange reactions showed straight lines. The slopes were steeper for Cs+ and Rb+ exchange reactions, as compared to K+ exchange. The cation-exchange selectivity for alkali metals was found to increase as follows: Cs+>Rb+>K+>Na+. A new evaluation method of the separation factor (αMN/KMd/KNd,Kd: distribution coefficient) for a combination of two cations at infinite dilution was proposed in terms of the selectivity coefficient (KMNa) which can be easily determined from the Kielland plot. An extremely large separation factor for Cs (αCsNa = 112) was found at infinite dilution. These basic studies of cation exchange selectivity are of relevance in cation separation and purification and nuclear waste disposal.
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Kuznetsova, Svetlana O., Kristina A. Mustafina, and Marina V. Takmakova. "THE RELATIONSHIP OF BODY MODIFICATION AND SELF-HARMING BEHAVIOR WITH PSYCHOLOGICAL TRAUMAS EXPERIENCED IN CHILDHOOD." Вестник Пермского университета. Философия. Психология. Социология, no. 3 (2022): 479–93. http://dx.doi.org/10.17072/2078-7898/2022-3-479-493.
Повний текст джерелаАнотація:
This article presents the results of empirical research on the relationship between body modification and self-harming behavior on the one hand and psychological trauma in childhood on the other hand. The problem appears to be topical due to the frequent occurrence of self-harming behavior and the increasing popularity of body modification. The hypotheses of the study were as follows: the extent of body modifi-cation and self-harm are positively associated with psychological traumas experienced in childhood; psy-chological traumas associated with violence experienced in childhood show a stronger correlation with body modification and self-harm in adulthood, compared with other types of psychological traumas. The study involved 105 women and 71 men aged 16 to 50 years (the average age of women was 21.5, the av-erage age of men was 25.2). The survey and subjective scaling methods were used. The analysis of rela-tionships between the variables was carried out with the help of nonparametric methods. The nonparamet-ric Spearman coefficient was used to study the correlation. The intergroup comparison of scale estimates was performed using a one-factor analysis of variance. We obtained statistically significant weak positive correlations between the number of body modifications and the overall indicator of adverse life events. The number of body modifications is significantly positively associated with the experience of family psycho-traumatic events and violence. The self-harm rate is significantly positively associated with the overall indicator of adverse life situations, experience of family psycho-traumatic situations and violence. The coefficients of correlation between self-harm and adverse life situations turned out to be slightly higher compared to the correlation between body modifications and adverse childhood experiences. Cor-relation analysis showed a weak but significant positive relationship between self-harm and the number of body modifications. Significant differences in the indicator of psycho-traumatic events were found be-tween subgroups of respondents with and without piercings. Respondents with piercings demonstrate sig-nificantly higher rates on the general scale of adverse life events, on the scale of family psycho-traumatic situations, and the scale of psycho-traumatic events related to violence, compared with respondents with-out piercings. Regression analysis showed a significant correlation between the coefficient of self-harm and the gender factor, the factor of family psycho-traumatic events and psycho-traumatic events related to violence. This model explained 16.2% of the variance of the self-injury coefficient. The number of body modifications was significantly related only to the gender factor and the factor of psycho-traumatic events related to violence, which explained only 7.4% of the variance in the number of body modifications.
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Zhu, Lei, Xiao-Yan Qi, Lamine Aoudjit, Flaviana Mouawad, Cindy Baldwin, Stanley Nattel, and Tomoko Takano. "Nuclear factor of activated T cells mediates RhoA-induced fibronectin upregulation in glomerular podocytes." American Journal of Physiology-Renal Physiology 304, no. 7 (April 1, 2013): F849—F862. http://dx.doi.org/10.1152/ajprenal.00495.2012.
Повний текст джерелаАнотація:
Glomerulosclerosis is featured by accumulation of the extracellular matrixes in the glomerulus. We showed previously that activation of the small GTPase RhoA in podocytes induces heavy proteinuria and glomerulosclerosis in the mouse. In the current study, we investigated the mechanism by which RhoA stimulates the production of one of the extracellular matrixes, fibronectin, by podocytes, specifically testing the role of nuclear factor of activated T cells (NFAT). Expression of constitutively active RhoA in cultured podocytes activated the fibronectin promoter, upregulated fibronectin protein, and activated NFAT. Expression of constitutively active NFAT in podocytes also activated the fibronectin promoter and upregulated fibronectin protein. RhoA-induced NFAT activation and fibronectin upregulation were both dependent on the calcium/calmodulin pathway and Rho kinase. NFAT activation was also observed in vivo in the rat and mouse models of podocyte injury and proteinuria, and NFAT inhibition ameliorated fibronectin upregulation in the latter. RhoA activation induced a rise of intracellular calcium ion concentration ([Ca2+]i), which was at least in part dependent on the transient receptor potential canonical 6 (TRPC6) cation channel. The results indicate that RhoA activates NFAT by inducing a rise of [Ca2+]i in podocytes, which in turn contributes to fibronectin upregulation. This pathway may be responsible for the pathogenesis of certain glomerular diseases such as hypertension-mediated glomerulosclerosis.
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Kozlova, Marina M., Artem E. Bobylev, Larisa N. Maskaeva, Vyacheslav F. Markov, and Maxim I. Smolnikov. "Catalytic oxidation of cation exchanger KU-2×8 with an aqueous solution of hydrogen peroxide." Butlerov Communications 58, no. 5 (May 31, 2019): 54–61. http://dx.doi.org/10.37952/roi-jbc-01/19-58-5-54.
Повний текст джерелаАнотація:
During the operation of nuclear power plants, spent ion-exchange resins are formed, which are heterogeneous radioactive low-level waste in the form of particles from a cross-linked organic polymer. Such resins may not always be regenerated. Therefore, the disposal of spent ion exchange resins is currently one of the primary problems at nuclear power plants. Conventional technologies for the processing of waste resins are relatively expensive. In addition, there are difficulties with transportation and storage of waste, and the disposal of spent ion exchange resins is a complex process. In the present study, an attempt has been made to solve the problem of spent ion-exchange resins utilization on example of the sulfonic acid cation exchanger’s KU-2×8 oxidative degradation with the Fenton reaction. The decomposition of the cation exchanger was carried out with 20% hydrogen peroxide in the temperature range 323-353 K in the presence of a catalyst – low concentration copper(II) sulfate (0.001-0.009 mmol/l). The influence of process temperature and catalyst concentration on the reaction rate was estimated. When determining the rate of the cation exchanger KU-2×8 heterogeneous oxidation reaction with hydrogen peroxide in the presence of a catalytic additive, the spherical shape of the sorbent granules, the surface area of which changed during reaction, was taken into account. It was shown that with a reaction temperature increasing from 323 to 353 K, the rate constant of cation exchanger's oxidative decomposition have increased by a factor of 20-37. The activation energy values of the sulfonic acid cation exchanger's KU-2×8 decomposition with hydrogen peroxide in the presence of copper(II) sulfate are 89.7-115.2 kJ/mol, which indicates that the process is in the kinetic mode. It was established with electron-microscopic studies that the beads of the cation exchanger KU-2×8, when decomposed in H2O2 solution in the presence of a catalyst can stick together, change their shape and volume, and their surface becomes covered with cracks. The studies performed showed almost complete catalytic decomposition of cation exchanger KU-2×8 in a hydrogen peroxide solution at 323-353 K after 420-220 minutes, which allows accelerating the oxidation at relatively low temperatures.
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Kajiwara, Moto, Tomohiro Terada, Jun-ichi Asaka, Masayo Aoki, Toshiya Katsura, Iwao Ikai, and Ken-ichi Inui. "Regulation of basal core promoter activity of human organic cation transporter 1 (OCT1/SLC22A1)." American Journal of Physiology-Gastrointestinal and Liver Physiology 295, no. 6 (December 2008): G1211—G1216. http://dx.doi.org/10.1152/ajpgi.90360.2008.
Повний текст джерелаАнотація:
Human organic cation transporter 1 (OCT1/SLC22A1) plays important roles in the hepatic uptake of cationic drugs. The functional characteristics of this transporter have been well evaluated, but molecular information regarding transcriptional regulation is limited. In the present study, therefore, we examined the gene regulation of OCT1 gene focusing on basal core expression. An ∼2.5-kb fragment of the OCT1 promoter region was isolated, and promoter activity was measured by luciferase assay in the human liver cell lines Huh7 and HepG2. Deletion analysis suggested that the region spanning −141/−69 was essential for the basal core transcriptional activity and that this region contained the sequence of a cognate E-box (CACGTG). The E-box is known to be bound by the basal transcription factors, upstream stimulating factors (USFs), and the functional involvements of USF1 and USF2 were confirmed by a transactivation effect, a mutational analysis of the E-box, and an electrophoretic mobility shift assay. The transactivation effect of USFs on the OCT1 promoter was further stimulated by hepatocyte nuclear factor 4α, a liver-enriched transcription factor. There were no polymorphisms in the proximal promoter region (about 400 bp) of OCT1 gene ( n = 109). These findings indicated that both USF1 and USF2 bind to an E-box sequence located in the OCT1 core promoter region and are required for the basal gene expression of this transporter.
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HUGHES, Gillian, Michael P. MURPHY та Elizabeth C. LEDGERWOOD. "Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor κB to modulate tumour necrosis factor-induced apoptosis: evidence from mitochondria-targeted antioxidants". Biochemical Journal 389, № 1 (21 червня 2005): 83–89. http://dx.doi.org/10.1042/bj20050078.
Повний текст джерелаАнотація:
ROS (reactive oxygen species) from mitochondrial and non-mitochondrial sources have been implicated in TNFα (tumour necrosis factor α)-mediated signalling. In the present study, a new class of specific mitochondria-targeted antioxidants were used to explore directly the role of mitochondrial ROS in TNF-induced apoptosis. MitoVit E {[2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl]triphenylphosphonium bromide} (vitamin E attached to a lipophilic cation that facilitates accumulation of the antioxidant in the mitochondrial matrix) enhanced TNF-induced apoptosis of U937 cells. In time course analyses, cleavage and activation of caspase 8 in response to TNF were not affected by MitoVit E, whereas the activation of caspase 3 was significantly increased. Furthermore, there was an increased cleavage of the proapoptotic Bcl-2 family member Bid and an increased release of cytochrome c from mitochondria, in cells treated with TNF in the presence of MitoVit E. We considered several mechanisms by which MitoVit E might accelerate TNF-induced apoptosis including mitochondrial integrity (ATP/ADP levels and permeability transition), alterations in calcium homoeostasis and transcription factor activation. Of these, only the transcription factor NF-κB (nuclear factor κB) was implicated. TNF caused maximal nuclear translocation of NF-κB within 15 min, compared with 1 h in cells pretreated with MitoVit E. Thus the accumulation of an antioxidant within the mitochondrial matrix enhances TNF-induced apoptosis by decreasing or delaying the expression of the protective antiapoptotic proteins. These results demonstrate that mitochondrial ROS production is a physiologically relevant component of the TNF signal-transduction pathway during apoptosis, and reveal a novel functional role for mitochondrial ROS as a temporal regulator of NF-κB activation and NF-κB-dependent antiapoptotic signalling.
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Titov, V. "Phylogenetic, structural and pathogenetic basis of classification of hypertension". "Arterial’naya Gipertenziya" ("Arterial Hypertension") 15, № 3 (28 червня 2009): 389–99. http://dx.doi.org/10.18705/1607-419x-2009-15-3-389-399.
Повний текст джерелаАнотація:
Classifi cations of clinical forms of arterial hypertension (AH) are based on differentiating its etiology; we propose a classifi cation that is based on the common pathogenesis of hydrodynamic pressure elevation in the intravascular pool of the intercellular medium, i.e., arterial blood pressure (BP). We believe that there are only three options for hydrodynamic pressure elevation in a mechanical model of the cardiovascular system: 1) a decrease in the arterial bed volume at a constant volume of the intravascular fl uid, 2) an increase in the volume of intravascular fl uid at a constant volume of the vascular bed and 3) an increased blood fl ow resistance at constant volumes of the vascular bed and intravascular fl uid. These options include all clinical forms of AH in which BP increases by common mechanisms. The fi rst option can be related to AH occurring in pheochromoblastoma, glucocorticoid hyperproduction and psychoemotional stress. The second is associated with AH developing in excessive NaCl consumption, increased aldosterone production in Conn syndrome (primary aldosteronism) and reduced production of atrial natriuretic peptide by phylogenetically modifi ed myocytes of the right atrium. The third option can be linked to all forms of increased peripheral blood fl ow resistance in the arterial bed presented at coarctation of the aorta, renovascular hypertension, impaired fl ow/endothelium-dependent vasodilation and moderate spasm of muscular arterioles, arterial wall atherosclerotic lesion (atheromatosis and atherothrombosis), Takayasu syndrome and obliterating endarteritis. BP elevation in erythremia, under the effect of leukocyte colony-stimulating factor and after injection of a recombinant erythropoetin can also be regarded within the frames of the third option. From the general biology viewpoint, all forms of AH developing against the background of impaired biological function of transcytosis (macropinocytosis) and crossing by food substrates and humoral mediators of bilayer structures between common and local pools of the intercellular medium, i.e., blood-brain barrier can be referred to as hematoencephalitic form. AH developing in impaired transcytosis across the bloodbrain barrier (endothelium + astrocytes bilayer) is an encephalopathic form; across endothelium + podocytes bilayer - renal form; endothelium + trophoblasts - placental AH; endothelium + pneumocytes - pulmonary AH; and endothelium + intimal macrophages - atherosclerosis-related AH. Normal BP points at the physiological level of transcytosis between all pools of the intercellular medium, the absence of peripheral blood fl ow resistance in the arterial bed, normal function of muscle arterioles, and the physiological levels of metabolic processes in all paracrine cell communities in vivo.
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Yang, Min, Sang Jung, Gautam Sethi, and Kwang Ahn. "Pleiotropic Pharmacological Actions of Capsazepine, a Synthetic Analogue of Capsaicin, against Various Cancers and Inflammatory Diseases." Molecules 24, no. 5 (March 12, 2019): 995. http://dx.doi.org/10.3390/molecules24050995.
Повний текст джерелаАнотація:
Capsazepine is a synthetic analogue of capsaicin that can function as an antagonist of TRPV1. Capsazepine can exhibit diverse effects on cancer (prostate cancer, breast cancer, colorectal cancer, oral cancer, and osteosarcoma) growth and survival, and can be therapeutically used against other major disorders such as colitis, pancreatitis, malaria, and epilepsy. Capsazepine has been reported to exhibit pleiotropic anti-cancer effects against numerous tumor cell lines. Capsazepine can modulate Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) pathway, intracellular Ca2+ concentration, and reactive oxygen species (ROS)-JNK-CCAAT/enhancer-binding protein homologous protein (CHOP) pathways. It can inhibit cell proliferation, metastasis, and induce apoptosis. Moreover, capsazepine can exert anti-inflammatory effects through the downregulation of lipopolysaccharide (LPS)-induced nuclear transcription factor-kappa B (NF-κB), as well as the blockage of activation of both transient receptor potential cation channel subfamily V member 1 (TRPV1) and transient receptor potential cation channel, subfamily A, and member 1 (TRPA1). This review briefly summarizes the diverse pharmacological actions of capsazepine against various cancers and inflammatory conditions.
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Gopinathan Nair, Amogh, Nick Rabas, Sara Lejon, Caleb Homiski, Michael J. Osborne, Normand Cyr, Aleksandr Sverzhinsky, et al. "Unorthodox PCNA Binding by Chromatin Assembly Factor 1." International Journal of Molecular Sciences 23, no. 19 (September 21, 2022): 11099. http://dx.doi.org/10.3390/ijms231911099.
Повний текст джерелаАнотація:
The eukaryotic DNA replication fork is a hub of enzymes that continuously act to synthesize DNA, propagate DNA methylation and other epigenetic marks, perform quality control, repair nascent DNA, and package this DNA into chromatin. Many of the enzymes involved in these spatiotemporally correlated processes perform their functions by binding to proliferating cell nuclear antigen (PCNA). A long-standing question has been how the plethora of PCNA-binding enzymes exert their activities without interfering with each other. As a first step towards deciphering this complex regulation, we studied how Chromatin Assembly Factor 1 (CAF-1) binds to PCNA. We demonstrate that CAF-1 binds to PCNA in a heretofore uncharacterized manner that depends upon a cation-pi (π) interaction. An arginine residue, conserved among CAF-1 homologs but absent from other PCNA-binding proteins, inserts into the hydrophobic pocket normally occupied by proteins that contain canonical PCNA interaction peptides (PIPs). Mutation of this arginine disrupts the ability of CAF-1 to bind PCNA and to assemble chromatin. The PIP of the CAF-1 p150 subunit resides at the extreme C-terminus of an apparent long α-helix (119 amino acids) that has been reported to bind DNA. The length of that helix and the presence of a PIP at the C-terminus are evolutionarily conserved among numerous species, ranging from yeast to humans. This arrangement of a very long DNA-binding coiled-coil that terminates in PIPs may serve to coordinate DNA and PCNA binding by CAF-1.
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Heinrich, Annette, Ulrike Böer, Mladen Tzvetkov, Elke Oetjen, and Willhart Knepel. "Stimulation by lithium of the interaction between the transcription factor CREB and its co-activator TORC." Bioscience Reports 29, no. 2 (January 21, 2009): 77–87. http://dx.doi.org/10.1042/bsr20080116.
Повний текст джерелаАнотація:
Lithium salts are clinically important drugs used to treat bipolar mood disorder. The mechanisms accounting for the clinical efficacy are not completely understood. Chronic treatment with lithium is required to establish mood stabilization, suggesting the involvement of neuronal plasticity processes. CREB (cAMP-response-element-binding protein) is a transcription factor known to mediate neuronal adaptation. Recently, the CREB-co-activator TORC (transducer of regulated CREB) has been identified as a novel target of lithium and shown to confer an enhancement of cAMP-induced CREB-directed gene transcription by lithium. TORC is sequestered in the cytoplasm and its nuclear translocation controls CREB activity. In the present study, the effect of lithium on TORC function was investigated. Lithium affected neither the nuclear translocation of TORC nor TORC1 transcriptional activity, but increased the promoter occupancy by TORC1 as revealed by chromatin immunoprecipitation assay. In a mammalian two-hybrid assay, as well as in a cell-free GST (glutathione transferase) pull-down assay, lithium enhanced the CREB–TORC1 interaction. Magnesium ions strongly inhibited the interaction between GST–CREB and TORC1 and this effect was reversed by lithium. Thus our results suggest that, once TORC has entered the nucleus, lithium as a cation stimulates directly the binding of TORC to CREB, leading to an increase in cAMP-induced CREB target-gene transcription. This novel mechanism of lithium action is likely to contribute to the clinical mood-stabilizing effect of lithium salts.
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Kuang, Xinyu, Qian Zhou, Zhuying Li, Yujie Hu, Yulin Kang та Wenyan Huang. "−254C>G SNP in the TRPC6 Gene Promoter Influences Its Expression via Interaction with the NF-κB Subunit RELA in Steroid-Resistant Nephrotic Syndrome Children". International Journal of Genomics 2019 (10 червня 2019): 1–7. http://dx.doi.org/10.1155/2019/2197837.
Повний текст джерелаАнотація:
This study is aimed at exploring the mechanism by which the −254C>G single nucleotide polymorphism (SNP) on the transient receptor potential cation channel 6 (TRPC6) gene promoter could increase its activation in steroid-resistant nephrotic syndrome children of China. Plasmids containing the TRPC6 promoter region (with the −254C or G allele) were constructed and then transfected into human embryonic kidney (HEK) 293T cells and human podocytes. Luciferase assays were used to test the promoter activity in both cell lines with or without tumor necrosis factor-α (TNF-α) treatment, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) analysis was used to verify the transcription factor that could bind to this mutant sequence. Luciferase results indicate that the activity of the mutant promoter was greater than that of the normal promoter of the TRPC6 gene in both cell lines. We further predicted and verified that this variation was mediated by the nuclear factor kappa B (NF-κB) subunit RELA, and TNF-α significantly enhanced the transcription activity of TRPC6 with the −254G allele. In conclusion, the −254C>G SNP is a gain-of-function variation of the TRPC6 gene, and it is also an early and effective factor for predicting steroid-resistant nephrotic syndrome (SRNS) in Chinese children.
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Penner, Glenn H., YC Phillis Chang, and H. Michelle Grandin. "A solid state NMR and molecular orbital study of hydroxylammonium chloride." Canadian Journal of Chemistry 77, no. 11 (November 1, 1999): 1813–20. http://dx.doi.org/10.1139/v99-156.
Повний текст джерелаАнотація:
Deuterium and nitrogen-15 NMR spectroscopy has been used to measure the 2H quadrupolar coupling and 15N chemical shift tensors in solid hydroxylammonium chloride, NH3OH+Cl-, (HAC). In addition, the NH3 and OH dynamics have been investigated by variable temperature 2H line shapes and T1 measurements. The Arrhenius activation energy for NH3 rotation is 22.5 ± 1.8 kJ/mol with a pre-exponential factor of 8 ± 3 × 1012 s-1 from line shapes and 21.3 ± 2 kJ/mol with an infinite temperature correlation time, τinf,, of 5.0 ± 0.4 × 10-14 s from the T1 analysis. The latter value corresponds to a pre-exponential factor of 6.7 ± 0.5 × 1012 s-1, if a three-site exchange is assumed. There was no evidence for OH reorientation up to 405 K, indicating a rather strong OH···Cl hydrogen bond. Previously reported inconsistencies between crystal structure and molecular orbital derived N-O bond lengths are cleared up by performing geometry optimizations with large basis sets and taking electron correlation into account. The internal rotational potential for the isolated HA cation is calculated to be 5.8 kJ/mol at the MP2/6-31G** level, with the trans geometry preferred. Calculations that employ the neutron diffraction geometry and include the Cl- anions that surround the HA+ cation yield an upper limit for the activation energy for NH3 group rotation of 62 kJ/mol. Analysis of the deuterium spectrum and T1 data yield nuclear quadrupolar coupling constants of 160 ± 5 kHz and 194 ± 5 kHz (η = 0.50 ± 0.05) for the ND3 and OD deuterons, respectively. Density functional calculations of the deuterium and nitrogen-14 nuclear quadrupolar coupling constants at the B3LYP level show that it is necessary to include the influence of the surrounding chloride anions. We have also shown that it is possible to obtain accurate proton chemical shifts from the deuterium MAS spectrum of solid HAC-d4.Key words: solid state NMR, molecular dynamics, nitrogen 15 chemical shift anisotropy.
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Xia, Shengqiang, Ying Liu, Xinming Li, Florian Thilo, and Martin Tepel. "Insulin Increases Expression of TRPC6 Channels in Podocytes by a Calcineurin-Dependent Pathway." Cellular Physiology and Biochemistry 38, no. 2 (2016): 659–69. http://dx.doi.org/10.1159/000438658.
Повний текст джерелаАнотація:
Background/Aims: Insulin signaling to podocytes is relevant for the function of the glomerulus. Now, we tested the hypothesis that insulin increases the surface expression of canonical transient receptor potential canonical type 6 (TRPC6) channels in podocytes by a calcineurin-dependent pathway. Methods: We used quantitative RT-PCR, immunoblotting, immunofluorescence and fluorescence spectrophotometry in cultured podocytes. Activation of Nuclear Factor of Activated T-cells (NFATc1) was measured using a specific calorimetric assay. Results: Insulin increased the expression of TRPC6 transcripts and protein in podocytes. Insulin increased TRPC6 transcripts in a time and dose-dependent manner. The insulin-induced elevation of TRPC6 transcripts was blocked in the presence of tacrolimus, cyclosporine A, and NFAT-inhibitor (each p < 0.01 by ANOVA and Bonferroni's multiple comparison test). Transcripts of NOX4, another target gene of the calcineurin-NFAT pathway, were affected in a similar way. Immunoblotting showed that the administration of 100 nmol/L insulin increased TRPC6-proteins 2-fold within 48 hours. Insulin increased the activity of NFATc1 in nuclear extracts (p < 0.001) whereas tacrolimus, cyclosporine A, and NFAT-inhibitor blocked that insulin effect (p < 0.001; two way ANOVA). Immunofluorescence showed that insulin increased TRPC6-expression on the cell surface. Fluorescence-spectrophotometry and manganese quench experiments indicated that the increased TRPC6-expression after insulin administration was accompanied by an elevated transplasmamembrane cation influx. Insulin-stimulated surface expression of TRPC6 as well as transplasmamembrane cation influx could be reduced by pretreatment with tacrolimus. Conclusion: Insulin increases the expression of TRPC6 channels in podocytes by activation of the calcineurin-dependent pathway.
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Vaitkevičius, Vitoldas, Ernestas Ivanauskas, Arminas Štuopys, and Mindaugas Daukšys. "MODIFYING THE COMPOSITION OF HOLLOW-CORE SLAB CONCRETE." Engineering Structures and Technologies 1, no. 1 (May 17, 2009): 58–64. http://dx.doi.org/10.3846/skt.2009.07.
Повний текст джерелаАнотація:
The questions of the extruded concrete composition and the possibilities of modifying it are very important for the technology for the extruded concrete. The gained experience of working with the extruders of hollow core slabs shows that the operators of such equipment frequently choose an improper strategy for the production process. The main drawbacks are as follows: a) the use of fairly stiff mixture that is far above the necessary Vebe consistency class V2 for this technology; b) the over saturation of the mixture with coarse aggregates which determines a low compaction factor of the mixture; c) the rejection of using concrete admixtures which causes equipment overloads or led to its exploitation in the limitary conditions. Besides, the experience of using extruders proves that all parameters predicted by standards and other norms (for example, concrete strength class C40/50 or C50/60 including water cement ratio W/C<0,45) are obtainable without large efforts. Therefore, the main criteria for the suitability of such concrete modifi cation have rather technological character including the lowest energy consumption during shaping and the compaction of the semi manufacture of the reinforced article as well as the highest structural strength or stability of the fresh concrete slab. Whereas the mechanical properties (mainly strength) of such hardened concrete are mostly within acceptable values, it cannot be treated as the main criterion for optimizing the extruded concrete composition. Extruded concrete compositions used for producing hollow-core slab were chosen for technological and laboratory scale investigations. The amount of Portland cement in the concrete mixture was 335…370 kg/m3, sand made 0/2 mm grade – 330…440kg/m3 and 0/4 mm grade – 680…510 kg/m3; the amount of coarse aggregates 200…325 kg/m3 and 755…825 kg/m3 for grades 2/8 mm and 11/16 mm respectively; W/C ratio 0,34…0,39. The crushing strength of the extruded concrete was within 57…68 MPa and more (the results of technological trials). The character of the structure and the compaction level of the extruded mixture are the indicators of its technological suitability. Adding common lignosulfonate-based plasticizer (up to 1% of the cement mass) or a very small dose (0,2…0,3%) of the new generation super plasticizer with or without air entrainment agent could improve the structural and technological properties of such concrete. The experience obtained during laboratory scale investigations and on trials for the manufacturing lines of hollow core slabs shows that the main cause of such improvements is a better dispersion of cement particles in the stiff concrete mixture while the cohesion of the mixture of the freshly extruded article rests near unchanged. The effectiveness of such improvement was proven within the process of observing the level of the consumption of compaction energy – it was registered by the control console of extruders. After improvements in the concrete mixture were carried out, the consumption of compaction energy was reduced by 20…25 %. Investigations into concrete cores drilled-out from the hardened articles prove the apparently better structure of the modifi ed concrete while concrete strength and other physical properties rests rather unchanged (if the mixture W/C ratio rests unchanged). Improvements to concrete structure manifests by the absence of ‘air pockets’ (large pores of irregular form, air gaps trapped during mixture extrusion and compaction), more gradually distributed and comparatively small pores, the absence of internal concrete structure zones with cleft aggregates and loose sand particles and evenly coloured concrete (which proves a very good distribution of cement particles). The use of an air entrainment agent in the stiff concrete mixture allows reducing the dose of the plasticizer (super plasticizer) and reduces the density and crushing strength of the extruded concrete. Such was negligible during investigation and technological trials (up to 1,5 % of concrete density and about 3 % of strength), it was concluded that the air entrainment agent could be used in the extruded concrete for articles the exploitation conditions of which are severe, for example, for class XF2 etc.
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Zhou, X., R. Ringseis, G. Wen та K. Eder. "The pro-inflammatory cytokine tumor necrosis factor α stimulates expression of the carnitine transporter OCTN2 (novel organic cation transporter 2) and carnitine uptake via nuclear factor-κB in Madin-Darby bovine kidney cells". Journal of Dairy Science 98, № 6 (червень 2015): 3840–48. http://dx.doi.org/10.3168/jds.2014-9044.
Повний текст джерела
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Jaikaew, Narisara, Rafael Auras, and Pakorn Opaprakasit. "Optimization of Melt-mixing Transesterifi cation of Polylactide by Polyethylene Glycol Employing Response Surface Methodology." Chiang Mai Journal of Science 49, no. 1 (January 31, 2022): 69–80. http://dx.doi.org/10.12982/cmjs.2022.006.
Повний текст джерелаАнотація:
A process for preparing polylactide-block-polyethylene glycol (PLA-b-PEG) copolymers has been developed and optimized by employing a transesterifi cation reaction in a melt-mixing process. The reaction was carried out in a counter-rotating mixer unit, using polyethylene glycol (PEG) and tetrabutyl titanate (TBT) catalyst. The effects of PEG weight percentage, catalyst contents, temperatures, and rotor speeds on chemical structures of the resulting PLA-b-PEG were examined, in terms of number average molecular weight (Mn), weight average molecular weight (Mw), in-chain PEG contents (wt.% PEG), and specifi c mechanical energy (SME) imparted by the mixer. The process parameters were optimized using a central composite rotatable design (CCRD) response surface methodology (RSM). The CCRD was designed with four variables at three levels of variations (-1, 0, -1), four replicates center point, and a redundancy factor (α) of 2.000. The responses (Mn, Mw, wt.% PEG, and SME) from 28 experimental trials were analyzed by a multiple linear regression fi tting, a second-order equation, and the RSM model. Mn and Mw of the products were determined by gel permeation chromatography (GPC). The in-chain PEG content was examined by nuclear magnetic resonance (1H-NMR) spectroscopy. The results show that the PEG weight percentage and the reaction temperature signifi cantly affect (P< 0.05) Mw and Mn of the products, which are drastically decreased with an increase in the PEG weight percentage and temperature. A quadratic interaction is observed between the PEG weight percentage and temperature, indicating that high reaction temperature leads to lower PEG conversions, due to undesirable competing thermal-oxidative degradations of PEG in the presence of the catalyst. Optimum operating conditions on the PEG weight percentage, catalyst contents, temperatures, and rotor speed for obtaining high Mw with high wt.% PEG was identifi ed. Although the optimal conditions are observed at the boundary level, the model serves as a platform for effective preparation of PLA-b- PEG copolymers with designed molecular weight and chemical structures. Further optimization of the model may be conducted by extending the range of independent factor levels. The resulting fl exible PLA-b-PEG copolymers, with tunable structures and properties, have high potential for use as singlecomponent degradable bioplastics with excellent mechanical properties, plasticizers, or toughening agent for enhancing PLA’s toughness.
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Parks, Alexandre, Xavier Charest-Morin, Michael Boivin-Welch, Johanne Bouthillier, and Francois Marceau. "Autophagic flux inhibition and lysosomogenesis ensuing cellular capture and retention of the cationic drug quinacrine in murine models." PeerJ 3 (October 6, 2015): e1314. http://dx.doi.org/10.7717/peerj.1314.
Повний текст джерелаАнотація:
The proton pump vacuolar (V)-ATPase is the driving force that mediates the concentration of cationic drugs (weak bases) in the late endosome-lysosome continuum; secondary cell reactions include the protracted transformation of enlarged vacuoles into autophagosomes. We used the inherently fluorescent tertiary amine quinacrine in murine models to further assess the accumulation and signaling associated with cation trapping. Primary fibroblasts concentrate quinacrine ∼5,000-fold from their culture medium (KM9.8 µM; transport studies). The drug is present in perinuclear granules that are mostly positive for Rab7 and LAMP1 (microscopy). Both drug uptake and retention are extensively inhibited by treatments with the V-ATPase inhibitor bafilomycin A1. The H+ionophore monensin also prevented quinacrine concentration by fibroblasts. However, inhibition of plasma membrane transporters or of the autophagic process with spautin-1 did not alter quinacrine transport parameters. Ancillary experiments did not support that low micromolar concentrations of quinacrine are substrates for organic cation transporters-1 to -3 or P-glycoprotein. The secondary autophagy induced by quinacrine in cells may derive from the accumulation of incompetent autophagolysosomes, as judged from the accumulation of p62/SQSTM1 and LC3 II (immunoblots). Accordingly, protracted lysosomogenesis is evidenced by increased expression of LAMP1 and LAMP2 in quinacrine-treated fibroblasts (48 h, immunoblots), a response that follows the nuclear translocation of the lysosomal genesis transcription factor TFEB and upregulation of LAMP1 and −2 mRNAs (24 h). Quinacrine administration to live mice evidenced variable distribution to various organs and heterogeneous accumulation within the lung (stereo-microscopy, extraction). Dose-dependentin vivoautophagic and lysosomal accumulation was observed in the lung (immunoblots). No evidence has been found for transport or extrusion mechanisms modulating the cellular uptake of micromolar quinacrine at the plasma membrane level. As shownin vitroandin vivo, V-ATPase-mediated cation sequestration is associated, above a certain threshold, to autophagic flux inhibition and feed-back lysosomogenesis.
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Zhang, H., and I. Farnan. "High temperature 35Cl nuclear magnetic resonance study of the LiCl–KCl system and the effect of CeCl3 dissolution." Faraday Discussions 190 (2016): 367–85. http://dx.doi.org/10.1039/c6fd00003g.
Повний текст джерелаАнотація:
This paper examines the dynamics of the LiCl–KCl system over a range of temperatures in order to understand the local structure surrounding chlorine, which is the common ion in these systems, during molten salt pyro-processing. Chlorine-35 nuclear magnetic resonance (NMR) is sensitive to the local environments of the resonant nuclei and their motion on a diffusive timescale. Thus, it is a good probe of the atomic scale processes controlling the viscosities, diffusivities and conductivities of these molten salts. The average isotropic chemical shifts (35Clδ) and spin-lattice relaxation times (T1) of 35Cl in (Li,K)Cl salt mixtures have been obtained over a compositional range of 0–100 mol% KCl with an interval of 10 mol% using high temperature nuclear magnetic resonance (NMR) spectroscopy from room temperature up to 890 °C. The 35Clδ in the two end member salts are consistent with the cation–anion radius ratio as previously measured on the solid halides and the average radius ratio of cation to anion, can be used to explain the variation of 35Clδ with composition. The quadrupolar interaction is found to be responsible for the spin-lattice relaxation of the 35Cl, and the activation energies for T1 relaxation have been obtained for all compositions. The measured T1 (35Cl) activation energies do not vary linearly with composition and peak at 50% KCl, which also coincides with the Chemla point for this system. They also are in good agreement with the values from equivalent conductivity measurements. To investigate the response of the system to solutes, 8 wt% of CeCl3 was added to the pure LiCl as a surrogate actinide. The shift induced was 120 ppm and the activation energy for the T1 (35Cl) increased by a factor of four. This is a promising preliminary result for probing the effect of actinide dissolution on the dynamics of these pyro-processing salts.
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Sen, P. N., C. Straley, W. E. Kenyon, and M. S. Whittingham. "Surface‐to‐volume ratio, charge density, nuclear magnetic relaxation, and permeability in clay‐bearing sandstones." GEOPHYSICS 55, no. 1 (January 1990): 61–69. http://dx.doi.org/10.1190/1.1442772.
Повний текст джерелаАнотація:
Based on measurements on some 100 sandstone core samples, mainly from oil fields from various parts of the world, we found the following regressions between volume‐to‐surface ratio [Formula: see text], permeability to fluid flow k, exchange cation molarity [Formula: see text], and proton NMR decay constant [Formula: see text] in water‐saturated rocks (see Figure 1): [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]. Here R is the regression coefficient, ϕ is the porosity and m the conductivity exponent; [Formula: see text] in normality (meq/ml), k in millidarcies, and [Formula: see text] in milliseconds, [Formula: see text] in μm. Including the tortuosity factor [Formula: see text] in conjunction with a pore‐size parameter as represented by [Formula: see text], [Formula: see text], or [Formula: see text] improves the correlation with permeability and reduces the residual error. The best predictor for log k is log [Formula: see text]. The exponents in the above correlations agree reasonably with those expected from simple models. These correlations provide a numerical basis for assessing how well some of these quantities can be estimated from others in log interpretation. They also provide a basis for assessing the importance of the factors that interfere with and thereby weaken the correlations.
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O’Brien, Valerie P., Kristin Bokelmann, Jacqueline Ramírez, Karoline Jobst, Mark J. Ratain, Jürgen Brockmöller, and Mladen V. Tzvetkov. "Hepatocyte Nuclear Factor 1 Regulates the Expression of the Organic Cation Transporter 1 via Binding to an Evolutionary Conserved Region in Intron 1 of the OCT1 Gene." Journal of Pharmacology and Experimental Therapeutics 347, no. 1 (August 6, 2013): 181–92. http://dx.doi.org/10.1124/jpet.113.206359.
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Go, Christina K., Robert Hooper, Matthew R. Aronson, Bryant Schultz, Taha Cangoz, Neeharika Nemani, Yi Zhang, Muniswamy Madesh, and Jonathan Soboloff. "The Ca2+ export pump PMCA clears near-membrane Ca2+ to facilitate store-operated Ca2+ entry and NFAT activation." Science Signaling 12, no. 602 (October 8, 2019): eaaw2627. http://dx.doi.org/10.1126/scisignal.aaw2627.
Повний текст джерелаАнотація:
Ca2+ signals, which facilitate pluripotent changes in cell fate, reflect the balance between cation entry and export. We found that overexpression of either isoform of the Ca2+-extruding plasma membrane calcium ATPase 4 (PMCA4) pump in Jurkat T cells unexpectedly increased activation of the Ca2+-dependent transcription factor nuclear factor of activated T cells (NFAT). Coexpression of the endoplasmic reticulum–resident Ca2+ sensor stromal interaction molecule 1 (STIM1) with the PMCA4b splice variant further enhanced NFAT activity; however, coexpression with PMCA4a depressed NFAT. No PMCA4 splice variant dependence in STIM1 association was observed, whereas partner of STIM1 (POST) preferentially associated with PMCA4b over PMCA4a, which enhanced, rather than inhibited, PMCA4 function. A comparison of global and near-membrane cytosolic Ca2+ abundances during store-operated Ca2+ entry revealed that PMCA4 markedly depressed near-membrane Ca2+ concentrations, particularly when PMCA4b was coexpressed with STIM1. PMCA4b closely associated with both POST and the store-operated Ca2+ channel Orai1. Furthermore, POST knockdown increased the near-membrane Ca2+ concentration, inhibiting the global cytosolic Ca2+ increase. These observations reveal an unexpected role for POST in coupling PMCA4 to Orai1 to promote Ca2+ entry during T cell activation through Ca2+ disinhibition.
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Hirata, Naoya, Shigeru Yamada, Shota Yanagida, Atsushi Ono, Yukuto Yasuhiko, Motohiro Nishida, and Yasunari Kanda. "Lysophosphatidic Acid Promotes the Expansion of Cancer Stem Cells via TRPC3 Channels in Triple-Negative Breast Cancer." International Journal of Molecular Sciences 23, no. 4 (February 10, 2022): 1967. http://dx.doi.org/10.3390/ijms23041967.
Повний текст джерелаАнотація:
Triple-negative breast cancer (TNBC) is a highly aggressive cancer for which targeted therapeutic agents are limited. Growing evidence suggests that TNBC originates from breast cancer stem cells (BCSCs), and elucidation of the molecular mechanisms controlling BCSC proliferation will be crucial for new drug development. We have previously reported that the lysosphingolipid sphingosine-1-phosphate mediates the CSC phenotype, which can be identified as the ALDH-positive cell population in several types of human cancer cell lines. In this study, we have investigated additional lipid receptors upregulated in BCSCs. We found that lysophosphatidic acid (LPA) receptor 3 was highly expressed in ALDH-positive TNBC cells. The LPAR3 antagonist inhibited the increase in ALDH-positive cells after LPA treatment. Mechanistically, the LPA-induced increase in ALDH-positive cells was dependent on intracellular calcium ion (Ca2+), and the increase in Ca2+ was suppressed by a selective inhibitor of transient receptor potential cation channel subfamily C member 3 (TRPC3). Moreover, IL-8 production was involved in the LPA response via the activation of the Ca2+-dependent transcriptional factor nuclear factor of activated T cells. Taken together, our findings provide new insights into the lipid-mediated regulation of BCSCs via the LPA-TRPC3 signaling axis and suggest several potential therapeutic targets for TNBC.
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Xu, Yuanyuan, Xirong Cao, Haoan Zhao, Erlin Yang, Yue Wang, Ni Cheng, and Wei Cao. "Impact of Camellia japonica Bee Pollen Polyphenols on Hyperuricemia and Gut Microbiota in Potassium Oxonate-Induced Mice." Nutrients 13, no. 8 (July 30, 2021): 2665. http://dx.doi.org/10.3390/nu13082665.
Повний текст джерелаАнотація:
Camellia japonica bee pollen is one of the major types of bee pollen in China and exhibits antioxidant and anti-inflammatory activities. The aims of our study were to evaluate the effects and the possible mechanism of Camellia japonica bee pollen polyphenols on the treatment of hyperuricemia induced by potassium oxonate (PO). The results showed that Camellia japonica bee pollen ethyl acetate extract (CPE-E) owned abundant phenolic compounds and strong antioxidant capabilities. Administration with CPE-E for two weeks greatly reduced serum uric acid and improved renal function. It inhibited liver xanthine oxidase (XOD) activity and regulated the expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1) and ATP-binding cassette superfamily gmember 2 (ABCG2) in kidneys. Moreover, CPE-E suppressed the activation of the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in PO-treated mice, and related inflammatory cytokines were reduced. CPE-E also modulated gut microbiota structure, showing that the abundance of Lactobacillus and Clostridiaceae increased in hyperuicemic mice. This study was conducted to explore the protective effect of CPE-E on hyperuricemia and provide new thoughts for the exploitation of Camellia japonica bee pollen.
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Cohen, A. E., B. M. Craven, and W. T. Klooster. "Structure and Thermal Vibrations of Spermine Phosphate Hexahydrate from Neutron Diffraction Data at 125K." Acta Crystallographica Section B Structural Science 53, no. 5 (October 1, 1997): 787–94. http://dx.doi.org/10.1107/s0108768197005892.
Повний текст джерелаАнотація:
Spermine phosphate hexahydrate crystallizes in space group P21/a with unit-cell dimensions a = 7.931 (1), b = 23.158 (5), c = 6.856 (2) Å, and \beta = 113.44 (2)° at 125 K with unit-cell contents [(C10H30N4)^{4+}_{2} (HPO4)^{2-}_{4}.12H2O]. The packing of spermines and monohydrogen phosphates in this crystal structure has features which may be relevant to the binding of spermine to DNA. Another important structural feature is the presence of channels containing water that is hydrogen bonded as in ice-Ih with disordered protons. The channels occur between sheets of spermine long chains and are also bordered by hydrogen-bonded monohydrogen phosphate chains. The hydrogen-bonding scheme of these water chains proposed on the basis of an earlier X-ray study is now confirmed. Nuclear positions, anisotropic mean-square (m.s.) displacements, an overall scale factor and two extinction parameters (\rho and g) were refined using full-matrix least-squares giving values of R(F^{2}_{o}) = 0.09, Rw(F^{2}_{o}) = 0.11 and S = 1.02. Thermal vibrational analysis revealed that the backbone of the spermine cation can be described as a single rigid segment with a substantial libration of 27 deg2 around the spermine molecular long axis.
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Maheshwari, Garima, Robert Ringseis, Gaiping Wen, Denise K. Gessner, Johanna Rost, Marco A. Fraatz, Holger Zorn, and Klaus Eder. "Branched-Chain Fatty Acids as Mediators of the Activation of Hepatic Peroxisome Proliferator-Activated Receptor Alpha by a Fungal Lipid Extract." Biomolecules 10, no. 9 (August 31, 2020): 1259. http://dx.doi.org/10.3390/biom10091259.
Повний текст джерелаАнотація:
The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated with the monomethyl BCFAs 12-methyltridecanoic acid (MTriA), 12-methyltetradecanoic acid (MTA), isopalmitic acid (IPA) and 14-methylhexadecanoic acid (MHD), and the direct activation of PPARalpha was evaluated by reporter gene assay using a PPARalpha responsive reporter gene. Furthermore, Fao cells were incubated with different concentrations of the CHLE and PPARalpha activation was also evaluated by using the reporter gene assay, and by determining the mRNA concentrations of selected PPARalpha target genes by real-time RT-PCR. The reporter gene assay revealed that IPA and the CHLE, but not MTriA, MHD and MTA, activate the PPARalpha responsive reporter gene. CHLE dose-dependently increased mRNA concentrations of the PPARalpha target genes acyl-CoA oxidase (ACOX1), cytochrome P450 4A1 (CYP4A1), carnitine palmitoyltransferase 1A (CPT1A) and solute carrier family 22 (organic cation/carnitine transporter), member 5 (SLC22A5). In conclusion, the monomethyl BCFA IPA is a potent PPARalpha activator. CHLE activates PPARalpha-dependent gene expression in Fao cells, an effect that is possibly mediated by IPA.
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Zhang, Han, Jie Ding, Qingfeng Fan та Shufang Liu. "RPC6 Up-Regulation in Ang II-Induced Podocyte Apoptosis Might Result from ERK Activation and NF-κB Translocation". Experimental Biology and Medicine 234, № 9 (вересень 2009): 1029–36. http://dx.doi.org/10.3181/0901-rm-11.
Повний текст джерелаАнотація:
Angiotensin II (Ang II) has been recognized as an apoptosis inducer in podocytes, but the mechanism of apoptosis induced by Ang II is unclear. Transient receptor potential cation channel 6 (TRPC6) is a calcium channel located in podocyte membrane. The present study evaluated the alteration of TRPC6 expression and the Ca2+ influx involved in Ang II-induced podocyte apoptosis. The possible pathways related to TRPC6 in Ang II-induced podocyte apoptosis were also investigated. The apoptosis of mouse podocytes (MPC5) was induced by Ang II. The protein level of TRPC6 was increased markedly in response to Ang II stimulation, and the intracellular Ca2+ concentration was elevated. By transfection with TRPC6 siRNA, Ang II-induced podocyte apoptosis and the transient Ca2+ influx were inhibited. Treated with extracellular signal-regulated kinase (ERK) pathway specific inhibitor U0126 or nuclear factor-κB (NF-κB) pathway specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and Ang II, respectively in podocytes, not only was the TRPC6 up-regulation reduced, but the podocyte apoptosis was also decreased. Moreover, the translocation of NF-κB in nucleus resulted from Ang II was reduced by treatment with U0126. In conclusion, the enhancement expression of TRPC6 as well as the increased Ca2+ influx mediated by TRPC6 channels contributed to the podocyte apoptosis. The activation of ERK pathway and subsequent translocation of NF-κB was possibly necessary for the up-regulation TRPC6 induced by Ang II.
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Park, Hyun-Jung, Malihatosadat Gholam-Zadeh, Jae-Hee Suh, and Hye-Seon Choi. "Lycorine Attenuates Autophagy in Osteoclasts via an Axis of mROS/TRPML1/TFEB to Reduce LPS-Induced Bone Loss." Oxidative Medicine and Cellular Longevity 2019 (October 8, 2019): 1–11. http://dx.doi.org/10.1155/2019/8982147.
Повний текст джерелаАнотація:
Lycorine, a plant alkaloid, exhibits anti-inflammatory activity by acting in macrophages that share precursor cells with osteoclasts (OCs). We hypothesized that lycorine might decrease bone loss by acting in OCs after lipopolysaccharide (LPS) stimulation, since OCs play a main role in LPS-induced bone loss. Microcomputerized tomography (μCT) analysis revealed that lycorine attenuated LPS-induced bone loss in mice. In vivo tartrate-resistant acid phosphatase (TRAP) staining showed that increased surface area and number of OCs in LPS-treated mice were also decreased by lycorine treatment, suggesting that OCs are responsible for the bone-sparing effect of lycorine. In vitro, the increased number and activity of OCs induced by LPS were reduced by lycorine. Lycorine also decreased LPS-induced autophagy in OCs by evaluation of decreased lipidated form of microtubule-associated proteins 1A/1B light chain 3B (LC3) (LC3II) and increased sequestosome 1 (p62). Lycorine attenuated oxidized transient receptor potential cation channel, mucolipin subfamily (TRPML1) by reducing mitochondrial reactive oxygen species (mROS) and decreased transcription factor EB (TFEB) nuclear translocation. Lycorine reduced the number and activity of OCs by decreasing autophagy in OCs via an axis of mROS/TRPML1/TFEB. Collectively, lycorine protected against LPS-induced bone loss by acting in OCs. Our data highlight the therapeutic potential of lycorine for protection against inflammatory bone loss.
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Hofman, J. P., A. de Kuijper, R. K. J. Sandor, M. Hausenblas, R. J. M. Bonnie, and T. W. Fens. "The Group III Shaly Sand Data Set." SPE Reservoir Evaluation & Engineering 1, no. 03 (June 1, 1998): 231–37. http://dx.doi.org/10.2118/39107-pa.
Повний текст джерелаАнотація:
Summary In the development of shaly sand saturation models, core data are of exceptional value. These data are required to check the descriptive and predictive power of existing models and compare them with new concepts. This paper aims to add to the modest set of generally available core data on shaly sands by presenting a variety of special core-analysis measurements on a number of shaly sand core samples. The experiments presented here include standard petrophysical measurements, continuous injection (CI) resistivity measurements (at ambient and elevated temperatures), nuclear magnetic resonance experiments (t1 and t2 acquisitions on fully brine-saturated samples; t2-diffusion measurements with an external magnetic gradient on partially brine-saturated samples), and scanning electron microscopy (SEM) images that have been subjected to image analysis. Introduction Whereas the number of theoretical models to describe the resistivity behavior of shaly sands is rather large, published data sets used to validate these models are scarce. This is hardly surprising if one realizes the amount of work that is involved, and the precision with which this work has to be carried out, to arrive at high-quality data. Examples of such data sets are the measurements on the Group 1 samples of Hill and Millburn, 1 Group II samples of Waxman and Smits,2 the high temperature results of Kern et al.,3 and the extensive clay property measurements of Hill et al.4 Information on the response of the conductivity of the samples at partial hydrocarbon saturations is missing from the aforementioned data sets. The Waxman and Thomas data set5 partially resolved this drawback with the presentation of C o-Cw curves at elevated temperatures in combination with resistivity index measurements at room temperature. However, the range in which the hydrocarbon saturations varied, from 0 to 50%, was rather limited. To arrive at a more complete set, shaly samples with various cation exchange capacities, originating from different wells, were selected for measurement of their electrical behavior at 100% brine saturation and at partial hydrocarbon saturation. The cation exchange capacity (Qv) of these samples ranges from 0.1 to 0.3 meq/mL pore volume (PV). SEM confirmed that the shale is not laminated in these samples; the clay minerals were not analyzed explicitly. Data from these samples form the currently presented Group III data set. This data set has formed the basis of the recently developed effective-medium saturation model SATORI.6* This article contains a host of relevant petrophysical and related properties obtained from the Group III sample set that can be used for testing shaly sand saturation models. The resistivity data presented here comprise resistivity index curves (at ambient temperature and some at elevated temperature), formation resistivity factors, and excess clay conductivities derived from concentration membrane potentials. Moreover, the nuclear magnetic resonance and SEM data provide more detail and information about the pore structure and constitution of the samples. The analyses were conducted with our routine procedures, as briefly outlined later. We have chosen a graphical presentation of the acquired data because of the size; however, if readers are interested in the digital form of the data set, they are invited to contact the first author. Standard Core Analysis Before each measurement, the samples were cleaned by hot solvent extraction at 52°C with an azeotropic mixture of chloroform/methanol/water. Subsequently, the samples were dried in a vacuum oven at 95°C. The porosity of the samples at ambient conditions was determined by the buoyancy method, both before and after the various special analyses. Before these, the air permeability of the samples was measured at a radial confining stress of 15 bar. Formation Resistivity Factor (F R). The samples were saturated with brine (100 g NaCl/L) and mounted individually in a Hassler-type core holder at a confining stress of 70 bar (the same stress as used for the resistivity index measurement). The sample was flushed with brine until equilibrium was reached in the resistance measurement. The resistivity of the brine was determined separately. From the resistivity of the 100% saturated sample, Ro, and the brine resistivity, Rw, the formation resistivity factor, FR=Ro/Rw, was calculated. Concentration Membrane Potential (Mc). The samples for measurement of the membrane potential were saturated with NaCl-brine of 8.4 g NaCl/L and mounted individually in a core holder.7 A salinity contrast was applied across the sample by alternating flushing one end-face of the sample with brine of 11.1 g NaCl/L and the other end-face with brine of 5.6 g NaCl/L. The equipment was maintained at 25°C during the experiment. The potential difference across the sample was recorded, and the maximum difference between this potential and the separately measured diffusion (or liquid junction) potential of the two brine solutions is a measure of the clay conductivity Ce (=B Qv) as defined in the Waxman-smits model.2 The factor, B, is the equivalent counter ion mobility, and the Qv is the cation exchange capacity of the clay per unit PV (Qv in meq/mL Vpore). The clay conductivity, Ce, is calculated from the difference between the membrane potential of a shaly sample and the liquid junction potential of the brine, and the difference between the potential of a perfect membrane (Nernst potential) and the liquid junction potential of the brine. The brine salinity and temperature determine the B-value, and the Qv of the sample can, hence, be derived. Wet Chemistry Cation Exchange Capacity (Qv). Cation exchange capacity (Qv) experiments were carried out according to a titration method, with barium chloride and magnesium sulfate as the reagents. The measurements are performed on trim-ends from the samples. The clean sample is crushed, and de-mineralized water and barium chloride are added. The clay present in the sample is converted into a monoionic barium clay. The excess barium is washed from the sample. Subsequently, the amount of barium present in the clay is titrated conductometrically with a standard magnesium sulfate solution. The calculated Q v value is expressed in meq/mL PV. Resistivity Measurements Standard CI Equipment. The sample is mounted in a Hassler-type core holder in a rubber sleeve between two plungers with platinum electrodes. A semipermeable membrane is placed between the sample and the bottom electrode.
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Lin, Brian Leei, Damian Matera, Julia F. Doerner, Nan Zheng, Donato del Camino, Sumita Mishra, Hong Bian, et al. "In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease." Proceedings of the National Academy of Sciences 116, no. 20 (April 26, 2019): 10156–61. http://dx.doi.org/10.1073/pnas.1815354116.
Повний текст джерелаАнотація:
Transient receptor potential canonical type 6 (TRPC6) is a nonselective receptor-operated cation channel that regulates reactive fibrosis and growth signaling. Increased TRPC6 activity from enhanced gene expression or gain-of-function mutations contribute to cardiac and/or renal disease. Despite evidence supporting a pathophysiological role, no orally bioavailable selective TRPC6 inhibitor has yet been developed and tested in vivo in disease models. Here, we report an orally bioavailable TRPC6 antagonist (BI 749327; IC50 13 nM against mouse TRPC6, t1/2 8.5–13.5 hours) with 85- and 42-fold selectivity over the most closely related channels, TRPC3 and TRPC7. TRPC6 calcium conductance results in the stimulation of nuclear factor of activated T cells (NFAT) that triggers pathological cardiac and renal fibrosis and disease. BI 749327 suppresses NFAT activation in HEK293T cells expressing wild-type or gain-of-function TRPC6 mutants (P112Q, M132T, R175Q, R895C, and R895L) and blocks associated signaling and expression of prohypertrophic genes in isolated myocytes. In vivo, BI 749327 (30 mg/kg/day, yielding unbound trough plasma concentration ∼180 nM) improves left heart function, reduces volume/mass ratio, and blunts expression of profibrotic genes and interstitial fibrosis in mice subjected to sustained pressure overload. Additionally, BI 749327 dose dependently reduces renal fibrosis and associated gene expression in mice with unilateral ureteral obstruction. These results provide in vivo evidence of therapeutic efficacy for a selective pharmacological TRPC6 inhibitor with oral bioavailability and suitable pharmacokinetics to ameliorate cardiac and renal stress-induced disease with fibrosis.
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Bertermann, R., and W. Müller-Warmuth. "Universality of NMR Results in LISICON Systems and Other Solid Lithium Conductors." Zeitschrift für Naturforschung A 53, no. 10-11 (November 1, 1998): 863–73. http://dx.doi.org/10.1515/zna-1998-10-1110.
Повний текст джерелаАнотація:
Abstract The temperature evolution of the 7Li NMR spectra and relaxation rates in many investigated solid lithium conductors shows more or less the same behavior. These compounds are characterized by a disordered lithium sublattice with a surplus of cation sites in cavities and channels of the anionic network. At low temperature, the spectra consist of a central line and a distributed satellite base structure. Upon increasing temperature, both components narrow until a reduced constant width with a well resolved quadrupole structure is reached. The mean nuclear quadrupole coupling parameters reduce by either about 5 or by a factor of 15 in all the compounds. The spin-lattice relaxation rates 1/T1 are asymmetric as a function of reciprocal temperature and of quadrupolar origin. The activation energy of the main process of ionic motion may best be obtained from the temperature dependence of the dipolar spin-spin-relaxation rate 1/T2 . The spectral densities of the relaxation dependences correspond to those for inhomogeneous motions; they may be described by modification of the BPP equation, a Cole-Davidson distribution or a Kohlrausch-Williams-Watts function. Within this study three LISICON systems, Li4-3x Gax GeO4 , and two phosphates Li3M2 (PO4)3 (M = Sc, In) were investigated or re-investigated which fit well into this scheme. Activation energies of 39-43 kJ/mol (Li4-3x Gax GeO4 with x = 0.06,0.14, 0.24), 53 kJ/mol (Li 3 Sc 2 (PO4)3) and 75 kJ/mol (Li3 In2 (PO4)3) were obtained.
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Abraham, E. H., J. L. Breslow, J. Epstein, P. Chang-Sing, and C. Lechene. "Preparation of individual human diploid fibroblasts and study of ion transport." American Journal of Physiology-Cell Physiology 248, no. 1 (January 1, 1985): C154—C164. http://dx.doi.org/10.1152/ajpcell.1985.248.1.c154.
Повний текст джерелаАнотація:
A method for analyzing individual mammalian cells with electron probe microanalysis has been developed using human diploid fibroblasts. Cells were grown on the same support that is used for experimental manipulations and analysis. Steady-state cation and anion concentrations and kinetic processes during experimental perturbations could be measured on populations of less than 1,000 cells. Human diploid fibroblasts in normal tissue culture medium had the following intracellular concentrations (in mM): K, 168; Na, 25.0; Cl, 51.2; P, 84.1; S, 16.5; Ca, 6.04; and Mg, 10.0. The ratios of K to Na were equivalent when measured in the nuclear or cytoplasmic area of the cells. Serum in the incubation medium was found to increase the cellular effective permeability to Na by a factor of 2.5, while leaving the effective permeability to K unchanged. When returned to control medium after 7 h of incubation in K-free medium, the cells recovered normal K/Na in less than 1 h. In some experiments the coupling ratio of the ouabain-inhibitable cellular transport of Na to K was 3:2 and the ratio of Cl to K was 1:2. The sum of intracellular content (Na + K) (an estimate of cellular volume) did not change when the cells were placed in K-free medium and increased by less than 30% after ouabain treatment. After 5-7 h of ouabain treatment or of incubation in K-free medium, long after the intracellular K had been replaced by Na, the cellular chloride content had not changed significantly.
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Ying, Rui, Zhaohui Zhang, Huiying Zhu, Bafang Li, and Hu Hou. "The Protective Effect of Mycosporine-Like Amino Acids (MAAs) from Porphyra yezoensis in a Mouse Model of UV Irradiation-Induced Photoaging." Marine Drugs 17, no. 8 (August 14, 2019): 470. http://dx.doi.org/10.3390/md17080470.
Повний текст джерелаАнотація:
The objective of this research was to extract and prepare mycosporine-like amino acids (MAAs) and investigate the mechanism by which they act against UV-induced skin photoaging in Institute of Cancer Research (ICR ) mice. MAAs such as porphyra-334 and shinorine were extracted from Porphyra yezoensis, separated, and purified using column chromatography with SA-2 cation exchange resin. The effects of MAAs on the activity of endogenous antioxidant enzymes, namely total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were analyzed in mouse skin tissue. Pathological changes of skin tissue caused by ultraviolet radiation and the arrangement of collagen were observed by Hematoxylin-Eosin (HE) staining and scanning electron microscopy (SEM). Interleukin 1β (IL-1β), IL-6, and IL-10 were detected using the quantitative real-time reverse transcription-polymerase chain reaction (qPCR) and Enzyme Linked Immunosorbent Assay (ELISA). The concentration and expression of these proinflammatory cytokines was associated with the presence of nuclear factor (NF)-κB. The results show that MAA compounds from Porphyra yezoensis could suppress UV-induced photoaging of skin by inhibiting the reduction of endogenous antioxidant enzymes. Compared to the control group, the concentrations of SOD, GSH-Px, and CAT increased significantly in skin tissue homogenate following the external administration of MAAs (p < 0.05, p < 0.01), while the content of MDA decreased significantly (p < 0.05). Meanwhile, the administration of MAAs was associated with down-regulations in the concentration and mRNA expression of NF-κB, IL-1β, IL-6, and IL-10. The results suggest that MAAs could protect skin from photodamage by increasing antioxidant enzyme activities and inhibiting inflammation.
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Luo, J., J. R. Ruble, B. M. Craven, and R. K. McMullan. "Effects of H/D substitution on thermal vibrations in piperazinium hexanoate-h11,d11." Acta Crystallographica Section B Structural Science 52, no. 2 (April 1, 1996): 357–68. http://dx.doi.org/10.1107/s0108768195011025.
Повний текст джерелаАнотація:
The crystal structures of piperazinium hexanoate-h11, {{1}\over{2}}C4H12N2+ 2.C6H11O− 2, and piperazinium hexanoate-d11, {{1}\over{2}}C4H12N2+ 2.C6D11O− 2, have been determined from neutron diffraction data collected at 15 K. Nuclear anisotropic displacement parameters have been analyzed to obtain the internal molecular displacements of the H and D nuclei, given by 〈 u 2 obs〉 − 〈 u 2 ext〉 where 〈 u 2 ext〉 is the contribution assuming all H/D to be carried rigidly on the vibrating molecular framework consisting of the heavier nuclei. In both crystal structures the cation ring is well fitted by the rigid-body model and the anion chain by a model with two rigid segments. In the piperazinium cations the corresponding protons in the two structures have about the same internal vibrational directions and magnitudes except for the two N—H protons, perhaps owing to differences in N—H...O hydrogen bonding. The internal vibrations of corresponding H/D in the h11 and d11 anions have approximately the same vibrational directions. The internal mean-square displacements of the H nuclei are systematically greater than the values of the corresponding D nuclei by an average factor 1.7 (3). For both anions, normal-mode analyses have been carried out using the force fields derived from ab initio quantum-mechanical calculations with HF/3-21 G and HF/6-31G** basis sets. The values of the resultant H/D internal displacements for C—H(D) bond stretching and methylene out-of-plane vibrations are in good agreement with experiment. However, with either basis set, theory predicts methylene in-plane mean-square displacements significantly greater than the experimental values.
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Elrasoul, Ahmed Shaaban Abd, Ahmed Abdelmoniem Mousa, Sahar Hassan Orabi, Mostafa Abd El-Gaber Mohamed, Shaban M. Gad-Allah, Rafa Almeer, Mohamed M. Abdel-Daim, Shaden A. M. Khalifa, Hesham R. El-Seedi, and Mabrouk Attia Abd Eldaim. "Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Effects of Azolla pinnata Ethanolic Extract against Lead-Induced Hepatotoxicity in Rats." Antioxidants 9, no. 10 (October 19, 2020): 1014. http://dx.doi.org/10.3390/antiox9101014.
Повний текст джерелаАнотація:
The current study investigated the protective potential of Azolla pinnate ethanolic extract (APE) against lead-induced hepatotoxicity in rats. Sixty male Wistar albino rats were randomly allocated into six groups (n = 10). The control group was orally administrated with saline. The second group received lead acetate (100 mg/kg body weight (BW) orally for 60 days). The third group was fed with APE (10 mg/kg BW orally for 60 days). The fourth group was administrated with lead acetate like the second group and APE like the third group, concomitantly, for 60 days. The fifth group was administrated with APE like the third group for 30 days, then orally administrated with the lead acetate like the second group for another 30 days. The sixth group was administrated with lead acetate like the second group for 30 days, then with APE like the third group for a further 30 days. Phytochemical analysis of APE indicated the presence of peonidin 3-O-glucoside cation, vitexin, rutin, thiamine, choline, tamarixetin, hyperoside, astragalin, and quercetin. The latter has been elucidated using one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) and liquid chromatography–mass spectrometry (LC–MS-MS). Lead acetate increased the serum levels of alanine and aspartate aminotransferases and that of urea, creatinine, tumor necrosis factor alpha, and interleukin 1β, hepatic tissue malondialdehyde contents, and caspase 3 protein expression, as well as altering the hepatic tissue architecture. However, it decreased the serum levels of interleukin 10 and glutathione (GSH) contents, and the activities of catalase and superoxide dismutase in hepatic tissue. In contrast, the administration of APE ameliorated the lead-induced alterations in liver function and structure, exemplifying the benefits of Azolla’s phytochemical contents. Collectively, A. pinnate extract is a protective and curative agent against lead-induced hepatotoxicity via its antioxidant, anti-inflammatory, and anti-apoptotic impacts.
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de Baaij, Jeroen H. F., Marian J. Groot Koerkamp, Marla Lavrijsen, Femke van Zeeland, Hans Meijer, Frank C. P. Holstege, René J. M. Bindels, and Joost G. J. Hoenderop. "Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg2+ handling." American Journal of Physiology-Renal Physiology 305, no. 11 (December 1, 2013): F1563—F1573. http://dx.doi.org/10.1152/ajprenal.00322.2013.
Повний текст джерелаАнотація:
The kidney plays a key role in the maintenance of Mg2+ homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg2+ handling. In recent years, hereditary Mg2+ transport disorders have helped to identify important players in DCT Mg2+ homeostasis. Nevertheless, several proteins involved in DCT-mediated Mg2+ reabsorption remain to be discovered, and a full expression profile of this complex nephron segment may facilitate the discovery of new Mg2+-related genes. Here, we report Mg2+-sensitive expression of the DCT transcriptome. To this end, transgenic mice expressing enhanced green fluorescent protein under a DCT-specific parvalbumin promoter were subjected to Mg2+-deficient or Mg2+-enriched diets. Subsequently, the Complex Object Parametric Analyzer and Sorter allowed, for the first time, isolation of enhanced green fluorescent protein-positive DCT cells. RNA extracts thereof were analyzed by DNA microarrays comparing high versus low Mg2+ to identify Mg2+ regulatory genes. Based on statistical significance and a fold change of at least 2, 46 genes showed differential expression. Several known magnesiotropic genes, such as transient receptor potential cation channel, subfamily M, member 6 ( Trpm6), and Parvalbumin, were upregulated under low dietary Mg2+. Moreover, new genes were identified that are potentially involved in renal Mg2+ handling. To confirm that the selected candidate genes were regulated by dietary Mg2+ availability, the expression levels of solute carrier family 41, member 3 ( Slc41a3), pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α ( Pcbd1), TBC1 domain family, member 4 ( Tbc1d4), and uromodulin ( Umod) were determined by RT-PCR analysis. Indeed, all four genes show significant upregulation in the DCT of mice fed a Mg2+-deficient diet. By elucidating the Mg2+-sensitive DCT transcriptome, new candidate genes in renal Mg2+ handling have been identified.
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Rios, Francisco J., Zhi-Guo Zou, Adam P. Harvey, Katie Y. Harvey, Ryszard Nosalski, Panagiota Anyfanti, Livia L. Camargo, et al. "Chanzyme TRPM7 protects against cardiovascular inflammation and fibrosis." Cardiovascular Research 116, no. 3 (June 28, 2019): 721–35. http://dx.doi.org/10.1093/cvr/cvz164.
Повний текст джерелаАнотація:
Abstract Aims Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg2+ homeostasis and vascular signalling. However, the pathophysiological significance of TRPM7 in the cardiovascular system is unclear. The aim of this study was to investigate the role of this chanzyme in the cardiovascular system focusing on inflammation and fibrosis. Methods and results TRPM7-deficient mice with deletion of the kinase domain (TRPM7+/Δkinase) were studied and molecular mechanisms investigated in TRPM7+/Δkinase bone marrow-derived macrophages (BMDM) and co-culture systems with cardiac fibroblasts. TRPM7-deficient mice had significant cardiac hypertrophy, fibrosis, and inflammation. Cardiac collagen and fibronectin content, expression of pro-inflammatory mediators (SMAD3, TGFβ) and cytokines [interleukin (IL)-6, IL-10, IL-12, tumour necrosis factor-α] and phosphorylation of the pro-inflammatory signalling molecule Stat1, were increased in TRPM7+/Δkinase mice. These processes were associated with infiltration of inflammatory cells (F4/80+CD206+ cardiac macrophages) and increased galectin-3 expression. Cardiac [Mg2+]i, but not [Ca2+]i, was reduced in TRPM7+/Δkinase mice. Calpain, a downstream TRPM7 target, was upregulated (increased expression and activation) in TRPM7+/Δkinase hearts. Vascular functional and inflammatory responses, assessed in vivo by intra-vital microscopy, demonstrated impaired neutrophil rolling, increased neutrophil: endothelial attachment and transmigration of leucocytes in TRPM7+/Δkinase mice. TRPM7+/Δkinase BMDMs had increased levels of galectin-3, IL-10, and IL-6. In co-culture systems, TRPM7+/Δkinase macrophages increased expression of fibronectin, proliferating cell nuclear antigen, and TGFβ in cardiac fibroblasts from wild-type mice, effects ameliorated by MgCl2 treatment. Conclusions We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7 and suggest that its protective effects are mediated, in part, through Mg2+-sensitive processes.
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Nabissi, Massimo, Massimo Offidani, Maria Beatrice Morelli, Manila Pettinari, Patrizia Caraffa, Silvia Gentili, Laura Corvatta, Giorgio Santoni, Francesco Alesiani, and Pietro Leoni. "TRPV2 Expression and Its Role in Proliferation of Human Multiple Myeloma Cell Lines." Blood 118, no. 21 (November 18, 2011): 5003. http://dx.doi.org/10.1182/blood.v118.21.5003.5003.
Повний текст джерелаАнотація:
Abstract Abstract 5003 Multiple myeloma (MM) is a disease typically characterized by repeated relapse that needs several new-drugs throughout its clinical course. Therefore, increasing knowledge of the pathways involved in the pathophysiology of MM will contribute to identified new therapeutic strategies. Specific signaling pathways as: nuclear factor kappa B (NFkB), farnelsyl-transferase (FTI), mitogenen-activated protein kinase (MAPK), proteosoma and others have been found to be disregulated in MM patients and cell lines. These findings have allowed the design of specific inhibitors that have been assessed in preclinical and clinical studies. Recent data have highlighted the contribute of ion channels (K+, Cl−, Na+ and Ca2+) in the regulation of cell proliferation, chemo-resistance, migration and invasion. Transient Receptor Potential Vanilloid type-2 (TRPV2) is a cation channel, member of the TRPV family, and its expression in human cancer cells and tissues has been reported for gliomas, prostate, bladder and pancreas, while no data were available in MM or in other hematological malignancies. TRPV2 expression has been found to influence cancer cell responses to chemo-therapeutic drugs as well as proliferation, migration and apoptosis, in part by increasing intracellular Ca2+ influx and/or by regulating specific signal pathways, like MAPK associated pathways. TRPV2 responds to noxious heat with an activation threshold of >52°C as well as to changes in osmolarity and membrane stretch; in addition, TRPV2 is activated by agonists such as 2-aminoethoxydiphenyl borate, as well as cannabinoids. The aim of this study was, firstly, to evaluate if TRPV2 was expressed in three human MM cell lines established models (RPMI, SKO-007, U266). Secondly we investigated on the role of TRPV2 activation in regulating the proteosoma inhibitor Bortezomib activity, in MM cell lines. By Real-Time PCR analysis we demonstrated that TRPV2 gene was expressed, with comparable relative levels, in the MM cell lines studied, and similar results were obtained at protein levels by Western blot analysis. Moreover, by immunofluorescence and FACS analysis we found that the percentage of TRPV2+ cells was 11% in RPMI, 3% in U266 and 2.6% in SKO-007. These data indicate that TRPV2 was expressed at low levels in MM cell lines. Since lost of TRPV2 expression was found to be associated with higher cell proliferation rate, in other tumor cell lines, and increasing of TRPV2 transcription and/or activity by specific agonists induced cell death and anti-proliferative effects, we evaluated the biological effects of TRPV2 activation in MM cell lines by MTT assay. The results showed that, after three incubation days, TRPV2 activation induced a decrease of cell viability of 70% in RPMI, 60% in U266 and 55% in SKO-007, compared to control. To evaluate if the reduced cell viability was dependent by an anti-proliferative and/or apoptotic process, the three cell lines treated with the TRPV2 agonist were analyzed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay for proliferation and by Annexin-V apoptosis assays. Data shown a decrease of BrdU+ cells in TRPV2 agonist treated cells (40% in RPMI, 30% in U266 and 28% in SKO-007) compared to control, while no significant differences were observed by Annexin-V analysis. Moreover, to evaluate a putative role of TRPV2 in influencing Bortezomib cytotoxicity, RPMI, SKO-007 and U266, were co-treated with the TRPV2 agonist in combination or not with Bortezomib, for three days. By a dose-response MTT analysis we determined that TRPV2 activation reduced MM cell lines viability more than 40% in RPMI, 20 % in U266 and 15% in SKO-007, compared to Bortezomib (5 ng/ml) alone. Summarizing, these preliminary data demonstrated that the TRPV2 cation channel was expressed in human MM cell lines and that activation of TRPV2 could play a role in increasing Bortezomib cytotoxicity, by inhibiting cell proliferation rather than increasing apoptosis of MM cells. These data may open new perspectives in combination therapy, albeit the molecular mechanisms undergone TRPV2 activation needs to be clarified. Disclosures: No relevant conflicts of interest to declare.
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Takahashi, Naoto, Matthew Brainbridge, Stuart A. Scott, Ryo Ichinohasama, Stephen E. Sanche, Wei-Feng Dong, John F. DeCoteau, and C. R. Geyer. "Identification of RIZ1 Targets Involvedin Erythroid Differentiation of K562 Human Erythroleukemia Cells Using Surface-Enhanced Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (SELDI)." Blood 104, no. 11 (November 16, 2004): 2031. http://dx.doi.org/10.1182/blood.v104.11.2031.2031.
Повний текст джерелаАнотація:
Abstract RIZ1 (PRDM2) is a member of the nuclear protein methyltransferase superfamily involved in chromatin remodeling. RIZ1 functions as a tumor suppressor gene in a number of human cancers and is down regulated in some human acute myeloid leukemias. We previously found RIZ-1 to be silenced in K562 erythroleukemia cells by promoter hypermethylation. Furthermore, expression of RIZ1 in K562 promotes erythroid differentiation and also potentiates TGF-β1 mediated differentiation. To investigate similarities between genes altered by RIZ1 expression and the TGF-β1 pathway, we used SELDI to compare the protein profiles of K562 against K562 + RIZ1 and K562 + TGF-β1. Protein extracts for SELDI profiling were separated into six fractions according to their isoelectric points. Proteins from each fraction were then bound to two different protein chip surfaces (H50-hydrophoboic and CM10-cation exhange) and their mass/charge determined using SELDI. We analyzed four replicates from each sample and classified proteins as differentially expressed if their P-values were below 0.05. In total, we observed 104 differentially expressed proteins (60 upregulated and 44 down regulated) between K562 and K562 + RIZ1 and 176 proteins (96 upregulated and 80 down regulated) between K562 and K562 + TGF-β1. We used 2D-PAGE to identify differentially expressed proteins identified by SELDI analysis and located 48 proteins that were over expressed in K562 + RIZ1 and K562 + TGF-β1 relative to K562. To establish whether these proteins were the same proteins observed using SELDI, we determined if the proteins had the same pI and molecular weight and if the gel-eluted proteins bound to the same protein chip surface with the same mass/charge. 15 of 48 proteins passed the above criteria and we determined their identities using Trypsin-based peptide mapping strategies with molecular weight and pI restrictions. We identified two candidate proteins (14-3-3ε and S100/A13) that are similarly over expressed in K562 + RIZ1 and K562 + TGF-β1. These proteins have been shown to be associated with TGF-β1 signaling. Schistosomal 14-3-3ε interacts with SmRK1, a divergent type I transforming growth factor β1 receptor (TR-I) present on the surface of adult parasites and also binds to and activates human TR-I. S100/A13 belongs to a family of low molecular weight proteins characterized by the presence of two calcium-binding EF-hand motifs that includes S100C/A11, a member recently shown to play a key role in a PKCα mediated pathway essential for the growth inhibition of normal human keratinocytes by TGF-β1. In summary, we demonstrate the potential for using SELDI to identify novel proteins involved in regulating and connecting cellular growth and differentiation pathways.
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Ateş, Esin, Nilgün Kizilcan, and Merve İstif. "New comonomer synthesis from thiophene-2-carbonyl chloride and cyclohexanone formaldehyde resin." Pigment & Resin Technology 44, no. 2 (March 2, 2015): 79–86. http://dx.doi.org/10.1108/prt-10-2013-0091.
Повний текст джерелаАнотація:
Purpose – The purpose of this paper is to synthesise an electro-active monomer containing ketonic resins and then to investigate the redox reaction between Fe+3 and bound thiophene in comonomer. First, thiophene-functionalised ketonic resins were synthesised by esterification reaction of thiophene-2-carbonyl chloride (ThCCl) and hydroxyl groups of cyclohexanone formaldehyde resin (CFR). Thiophene-containing cyclohexanone formaldehyde resin (Th-CFR) was then polymerised by ferric salt. The structures of the specimens were characterised by means of Fourier transform infrared and Proton – Nuclear Magnetic Resonanse (1H-NMR) spectroscopy. Thermal properties of the samples were determined with differential scanning calorimeter. Molecular weights of the specimens were determined by gel permeation chromatography. The obtained samples were also characterised morphologically by scanning electron microscope. Design/methodology/approach – Synthesis of Th-CFR comonomers by a combination of condensation polymerization and chemical oxidation polymerisation processes is described. First, Th-CFR units were prepared by direct condensation reaction of thiophene-2-carbonyl chloride (ThCCl) and hydroxyl groups of CFR. Then, the chemical oxidation (CO) of Th-CFR in the presence of anhydrous iron (III) chloride salt (FeCl3) was performed in chloroform (CHCl3)/acetonitrile mixture solutions at room temperature. Findings – The important structural factor determined quantitatively for Th-CFR is the CFR/ThCCl ratio after reaction. The effect of the mole ratio effect of ThCCl and ketonic resin on the solubility, molecular weight, Tm and Tg values of the comonomers (Th-CFRs) were investigated. Research limitations/implications – The ferric ion (Fe+3) has a standard oxidation potential. Furthermore, FeCl3 can react with thiophene to produce a cation radical. FeCl3 cannot react with hydroxyl groups of ketonic resins. When ferric is used for in situ chemical oxidation application at relatively low temperatures (e.g. < 20°C), the oxidation reactions are usually less aggressive. Practical implications – This work provides technical information for the synthesis of conducting block copolymer and for the synthesis of chain-extended resins. The modified resins contain electro-active monomer as thiophene. The chemical oxidation system has been used to polymerise these thiophene groups and resins with much higher molecular weight might be produced. These resins may also promote the adhesive strength of a coating and corrosion inhibition to metal surfaces of a coating. Social implications – This will be used for the preparation of AB- and ABA-type block copolymers. These block copolymers may exhibit different properties due to incorporation of monomer into the block copolymer structure. Originality/value – Novel Th-CFR comonomers were synthesised. These comonomers have higher glass transition temperature (Tg) and melting temperature (Tm) value than CFR alone. The chemical oxidation system has been used to polymerise these thiophene-functionalised ketonic resins.
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Al-Muntasheri, Ghaithan A., Hisham A. Nasr-El-Din, and Pacelli L. J. Zitha. "Gelation Kinetics and Performance Evaluation of an Organically Crosslinked Gel at High Temperature and Pressure." SPE Journal 13, no. 03 (September 1, 2008): 337–45. http://dx.doi.org/10.2118/104071-pa.
Повний текст джерелаАнотація:
Summary Organically crosslinked gels have been used to control water production in high temperature applications. These chemical systems are based on the crosslinking of a polyacrylamide-based polymer/copolymer with an organic crosslinker. Polyethyleneimine (PEI) has been used as an organic crosslinker for polyacrylamide-based copolymers to provide thermally stable gels. Literature reported that PEI can form aqueous gels with polyacrylamide (PAM) at room temperature. In this paper, we show for the first time the possibility of crosslinking polyacrylamide with PEI at temperatures up to 140°C (285°F) and pressures up to 30 bars (435 psi). This paper reports data both in bulk and in porous media. The gelation time of the PAM crosslinked with PEI at high temperatures up to 140°C (285°F) and pressures up to 435 psi (30 bars) was measured. The effects of polymer concentration, crosslinker concentration, temperature, salinity, initial pH value, and the initial degree of hydrolysis of the polymer on the gelation time were examined in detail. All measurements were conducted in the steady shear mode. 13C Nuclear Magnetic Resonance Spectroscopy (13C NMR) was used to relate the gelation time to changes in the structure of the polymer and hence explain the variation in the gelation time in terms of the gelling system chemistry. In bulk, thermally stable gels were obtained by crosslinking PAM with PEI at 130°C (266°F) for at least 8 weeks. The performance of the PAM/PEI system in sandstone cores at a temperature of 90°C (194°F) and pressure drops of 68.95 bars (1,000 psi) was examined. The system was found to be stable for 3 weeks, where the permeability was reduced by a factor of 100%. Introduction Water production is a serious problem in petroleum-producing operations. Additional costs are imposed by processing, treating, and disposing unwanted water. Of the available remediation techniques, chemical methods using polymer gels have been widely applied. The success rate of these chemical treatments depends, among other factors, on the understanding of gelation kinetics, gelant's compatibility with reservoir fluids, and thermal stability of the final gel. Polymer gels have been used to reduce water production through the disproportionate permeability reduction (DPR) (Zaitoun and Kohler 1988; Liang et al. 1995). In DPR, the relative permeability to water is reduced to a greater extent than that to oil (or gas). Polymer gels were also used to totally block the pore space of the water producing zones in both matrix (Vasquez et al. 2003) and fractures (Alqam et al. 2001). Polymer gels are generally classified into two categories based on the nature of polymer/crosslinker bonding chemistry. The first type is inorganic gel systems based on the crosslinking of the carboxylate groups on the partially hydrolyzed polyacrylamide chain (PHPA) with a trivalent cation like Cr(III) (Sydansk 1990; Lockhart 1994). This crosslinking is believed to rely on coordination covalent bonding. It should be mentioned that Cr(III)-carboxylate/acrylamide-polymer gels (CC/AP) were reported to be stable at temperatures up to 148.9°C (300°F) in Berea cores under pressure drops of 68.95 bars (1,000 psi) (Sydansk and Southwell 2000). The second class of polymer gels is based on covalent bonds between the crosslinker and the acrylamide-based polymer (Morgan et al. 1998; Moradi-Araghi 2000). High temperature applications require the use of thermally stable covalently bonded systems. However, these covalent bonds do not guarantee long-term stability. Literature reports (Moradi-Araghi 2000) highlight the importance of using a thermally stable polymer to produce thermally stable gels. Polyacrylamide-based polymers are known to hydrolyze at high temperatures causing gel syneresis (expulsion of water out of the gel structure due to over crosslinking) (Moradi-Araghi 2000), especially in brines with high contents of Mg+2 and Ca+2, where polymer precipitation may also occur (Moradi-Araghi and Doe 1984). Therefore, more thermally stable monomers are copolymerized with the acrylamide polymer to minimize excessive hydrolysis (Moradi-Araghi et al. 1987; Doe et al. 1987) and enhance thermal stability of the produced gel.
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Wang, Jueqiong, Chung Hoow Kok, Richard J. D'Andrea, Timothy P. Hughes та Deborah L. White. "Role Of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and Its Ligands In The Regulation Of Functional OCT-1 Activity In CML Cells". Blood 122, № 21 (15 листопада 2013): 1470. http://dx.doi.org/10.1182/blood.v122.21.1470.1470.
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Abstract Introduction The human organic cation transporter-1 (hOCT-1) is the primary active influx protein for imatinib in BCR-ABL positive cells. The functional activity of the OCT-1 protein (OCT-1 activity, OA) is predictive of molecular response in de-novo chronic phase chronic myeloid leukemia (CP-CML) patients. We have previously demonstrated that diclofenac, a competitive peroxisome proliferator-activated receptor-γ (PPARγ) antagonist, can significantly increase OA in CML cells 1. However, the role of PPARγ and its ligands in OA regulation remain unknown. Thus, the link between OA and PPARγ in CML cells has been investigated in this study. Methods OA was determined by intracellular uptake and retention assay (IUR) in the presence and absence of the OCT-1 inhibitor, prazosin 2. To assess the effect of PPARγ ligands on OA, BCR-ABL positive cell lines (KU812, K562) were incubated with PPARγ antagonist (GW9662, T0070907) or agonists (GW1929, rosiglitazone) respectively for 1 hour immediately prior to the IUR assays. The OA was also assessed in the mononuclear cells (MNCs) of 77 CP-CML patients enrolled to the TIDEL II trial. PPARγ activity in CML MNC nuclear extracts was determined through the use of a PPARγ Transcription Factor Assay Kits according to the manufacturer's instructions. To assess the effect of PPARγ ligands on cell death, KU812 or K562 cells were stained with AnnexinV and 7-AAD for detection of apoptosis after the co-administration of imatinib and PPARγ ligands for 72 hours. Results A significant increase in OA was observed in KU812 and K562 cells treated with PPARγ antagonists. In contrast, PPARγ agonists significantly decreased the OA in both cell lines (Table 1). A negative link between OA and PPARγ activity was observed in CML MNC samples (R=-0.585, p<0.001). PPARγ activity was significantly elevated in CML patients who had a low OA at diagnosis (less than 4 ng/200,000 cells) compared with those who had higher OA (p<0.001). After 72 hours co-administration with 0.1µM imatinib, KU812 cells treated with PPARγ antagonists (GW9662 and T0070907) showed a significantly lower cell viability (40% and 18% respectively) compared with vehicle control (70%, p<0.001). Similar results were also observed in K562 cells after co-administration with 1.0µM imatinib for 72 hours. K562 cells treated with PPARγ antagonists (GW9662: 51% and T0070907: 47%) showed a significantly lower cell viability (51% and 47% respectively) compared with vehicle control (61%, p<0.05). Conclusion Ligand-activation or inhibition of PPARγ is a regulator of OA in CML cell lines, and the low MNC OCT-1 activity in CML patients is consistent with the high level of PPARγ activity in these cells. Low PPARγ activity may be the key driver for low OA and poor imatinib response observed in a subset of CML patients. Importantly, the enhanced OA as a result of PPARγ antagonist treatment resulted in increased cell death following co-administration with imatinib. Ongoing studies relating to the upstream pathways involved in PPARγ activation aim to reveal the possible mechanism of OA modulation by PPARγ. Enhancement of OA by PPARg antagonists is likely to provide an important axis for clinical application to improve the clinical efficacy of imatinib. This would be particularly important in patients with low OA who currently have inferior outcomes with imatinib therapy. 1. Wang J, Hughes TP, Kok CH, et al. Contrasting effects of diclofenac and ibuprofen on active imatinib uptake into leukaemic cells. British Journal of Cancer. 2012;106(11):1772-1778. 2. White DL, Saunders VA, Dang P, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: Higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood. 2007;110(12):4064-4072. Disclosures: Hughes: Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; CSL: Research Funding. White:Novartis: Research Funding; BMS: Research Funding, Speakers Bureau; Ariad: Research Funding; CSL: Research Funding.
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Minh, Chanh Cao, Robert Freedman, Steve Crary, and Darrel Cannon. "Integration of NMR With Other Openhole Logs for Improved Formation Evaluation." SPE Reservoir Evaluation & Engineering 3, no. 06 (December 1, 2000): 509–16. http://dx.doi.org/10.2118/68208-pa.
Повний текст джерелаАнотація:
Summary The recently introduced measurement of total porosity from nuclear magnetic resonance (NMR) tools can help to identify the hydrocarbon type and to improve the determination of formation total porosity (?t) and water saturation (Swt) in combination with other openhole logs. In shaly formations, porosities are difficult to estimate in the presence of hydrocarbons, especially those for gas and light oils. Water saturations are even more difficult to estimate because critical parameters such as clay cation exchange capacities/unit pore volume (QV), the formation factor (F) and formation water resistivity (Rw) might not be known. The latter quantities are essential inputs into the Waxman-Smits and dual-water model saturation equations. In the typical case of shaly gas-bearing formations, both the total porosity corrected for the gas effect and the gas saturation (Sxgas) in the flushed zone can be derived by combining total NMR porosity (?NMR) and density porosity (?density) Adding resistivity logs such as Rxo) and Rt helps to differentiate between gas and oil. Furthermore, the flushed zone water saturation (Sxot) computed from 1?Sxgas can be used in many ways. One procedure uses Sxot in conjunction with the Rxo saturation equation to determine QV or F. Another technique uses Sxot in conjunction with the saturation point (SP) to estimate QV when Rw is known. Yet, another method estimates QV directly from the NMR short relaxation time part of the T2 distribution and use Sxot in conjunction with SP to estimate Rw. The new interpretation procedure follows the sequential shaly sands approach: first, determine porosity, second, determine shaliness, and, third, determine saturation. The new procedure improves on the classical method by offering new ways to compute QV, F and Rw, The methodology is applied to a number of field examples. Introduction Recently, Freedman et al. have shown how to combine ?NMR and ?density to estimate the gas-corrected total porosity ?t and the flushed zone gas saturation in the density magnetic resonance (DMR) method.1 In this paper we build upon their work and integrate NMR logs with other openhole logs in new ways to improve formation evaluation. For hydrocarbon identification, two simple techniques that combine total NMR porosity, density, shallow and deep resistivity logs are shown in a field example. The techniques are simple enough to give a real-time answer when NMR is logged in combination with the above logs. For water saturation determination, total porosity corrected for the hydrocarbon effect and QV is essential. Classical shale sand log analysis first estimates porosity from the density neutron, then corrects for the hydrocarbon effect using Sxot from an Rxo tool in an iterative loop.2 The DMR method does not require any iteration since the linear forms of the density and NMR response equations provide an exact analytical solution of the flushed zone total porosity and saturation. Sxot can then be used in conjunction with an Rxo tool to compute other petrophysical parameters such as QV or F. On the other hand, quantitative use of the SP log in shale sand log analysis was demonstrated by Smits3 in 1968. Integrating SP with NMR and other openhole logs allows the estimation Rw or QV in a two-step SP inversion procedure.4 Both the above techniques to determine QV are applied to a field example. In a second field example, NMR and SP logs are used to compute varying Rw in a fresh water example using continuous QV estimated directly from the NMR short T2 time distribution. The new interpretation methodology is readily extendable to complex lithology, although a multitools solver approach such as the ELAN™ processing method might be preferred.5 (ELAN is a trademark of Schlumberger.) Quicklook Hydrocarbon Identification Gas identification with the DMR method is unambiguous when the deficit between density porosity and total NMR porosity is large [e.g., 6 pore units (p.u.) or more]. When the deficit is not large (a few p.u.), one is not sure whether light oil is present or some gas remains in the pore space after flushing. Because the DMR results depend on the input (gas or light oil), of hydrocarbon type whereas the shallow resistivity does not (it only sees the water phase), it is possible to determine the hydrocarbon type by simply comparing the DMR results with the Rxo results. Rxo?Rt Method A simple method is to compare the flushed zone water saturation determined by the DMR method with the flushed zone water saturation determined from the Rxo tool. If the two saturations agree (meaning that the DMR gas hypothesis is correct) and the Rt tool indicates hydrocarbon, then the hydrocarbon is gas. If the two saturations disagree (meaning that the DMR gas hypothesis is incorrect) and the Rt tool indicates hydrocarbon, then the hydrocarbon is light oil. In the zones where Swt<0.7 (a given saturation cutoff), hydrocarbon is present, and if Sxot, DMR-gas? Sxot, Rxo, then gas or light oil is present.
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Zhong, Weiting, Mingming Ma, Jingwen Xie, Chengcui Huang, Xiaoyan Li, and Min Gao. "Adipose-specific deletion of the cation channel TRPM7 inhibits TAK1 kinase-dependent inflammation and obesity in male mice." Nature Communications 14, no. 1 (January 30, 2023). http://dx.doi.org/10.1038/s41467-023-36154-3.
Повний текст джерелаАнотація:
AbstractChronic inflammation of white adipose tissue is a key link between obesity and the associated metabolic syndrome. Transient receptor potential melastatin-like 7 (TRPM7) is known to be related to inflammation; however, the role of TRPM7 in adipocyte phenotype and function in obesity remains unclear. Here, we observe that the activation of adipocyte TRPM7 plays an essential role in pro-inflammatory responses. Adult male mice are used in our experiments. Adipocyte-specific deficiency in TRPM7 attenuates the pro-inflammatory phenotype, improves glucose homeostasis, and suppresses weight gain in mice fed a high-fat diet. Mechanistically, the pro-inflammatory effect of TRPM7 is dependent on Ca2+ signaling. Ca2+ influx initiated by TRPM7 enhances transforming growth factor-β activated kinase 1 activation via the co-regulation of calcium/calmodulin-dependent protein kinase II and tumor necrosis factor receptor-associated factor 6, leading to exacerbated nuclear factor kappa B signaling. Additionally, obese mice treated with TRPM7 inhibitor are protected against obesity and insulin resistance. Our results demonstrate TRPM7 as a factor in the development of adipose inflammation that regulates insulin sensitivity in obesity.
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Holland, Diane, Ben G. Parkinson, Moinul M. Islam, Adam Duddridge, Jonathan M. Roderick, Andy P. Howes, and Charlie R. Scales. "NMR Investigation of Cation Distribution in HLW Wasteform Glass." MRS Proceedings 1107 (2008). http://dx.doi.org/10.1557/proc-1107-199.
Повний текст джерелаАнотація:
AbstractMagic-angle-spinning NMR has been used to establish the structural roles of various cations added to the borosilicate glass which is used for the vitrification of high-level nuclear waste (HLW). Representative surrogate oxides with nominal valencies of +1, +2 and +3 have been studied which span the range of oxides from modifier to intermediate and conditional glassformer. NMR has been carried out on those nuclei which are accessible and the species observed have been correlated with the physical and chemical behaviour. The controlling factor is the manner in which the alkali cations partition between the various network groups, changing the distribution of silicon Qn species and the boron N4 ratio. Identifiable superstructural units are also present in these glasses. The aqueous corrosion rate increases with Q3 content, as does the weight loss due to evaporation from the melt. The activation energy for DC conduction scales with N4. Values of N4 obtained for these glasses deviate significantly from those predicted by the currently accepted model (Dell and Bray) and are strongly affected by the modifier or intermediate nature of the surrogate oxide and also by its effect on the distribution of nonbridging oxygens between the silicate and borate polyhedra.
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Woldegabriel, G., and S. Levy. "Ion Exchange and Dehydration Effects on Potassium and Argon Contents of Clinoptilolite." MRS Proceedings 412 (1995). http://dx.doi.org/10.1557/proc-412-791.
Повний текст джерелаАнотація:
AbstractZeolite-rich Miocene tuffs are an important part of the principal hydrochemical barrier to water-borne radionuclide transport from a potential high-level nuclear waste repository at Yucca Mountain, Nevada. The timing of zeolitization is an issue that relates to paleohydrology, permeability, zeolite stability, and unsaturated-zone geochemical processes. Exploratory K/Ar dating of clinoptilolite, the most abundant and widespread zeolite, shows a striking and consistent pattern of increasing apparent ages (2–13 Ma) with depth. Only the isotopic ages from the saturated zone are compatible with geologic evidence suggesting an age >10 Ma for most of the zeolites.Factors that may be responsible for the young apparent ages in the unsaturated zone were investigated. Cation exchange with recharge water and Ar diffusion under unsaturated conditions (processes that may be characteristic of the unsaturated zone) were evaluated experimentally for their effects on K/Ar systematics. Cation exchanging a natural clinoptilolite with Ca-, Cs-, K-, and Na-chloride solutions showed minimal effects on radiogenic Ar content. However, clinoptilolite heated at 2007deg;C for 16 hours in air lost a significant amount of its radiogenic Ar compared with minimal losses from clinoptilolite heated in water at 100°C for over 5 months. The preliminary results indicate that Ar loss from incompletely hydrated clinoptilolite may be a major factor contributing to the young apparent ages of clinoptilolite in the unsaturated zone at Yucca Mountain.